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BACKGROUND Coronary vasomotor dysfunction can be diagnosed in a large proportion of patients with angina in the presence of non-obstructive coronary artery disease (ANOCA) using comprehensive protocols for coronary vasomotor function testing. Although consensus on diagnostic criteria for endotypes of coronary vasomotor dysfunction have been published, consensus on a standardised study testing protocol is lacking. AIMS In this review we provide an overview of the variations in coronary vasomotor function testing used and discuss the practical principles and pitfalls of coronary vasomotor function testing. METHODS For the purpose of this review we assessed study protocols that evaluate coronary vasomotor response as reported in the literature. We compared these protocols regarding a number of procedural aspects and chose six examples to highlight the differences and uniqueness. RESULTS Currently, numerous protocols co-exist and vary in vascular domains tested, the manner to test these domains (e.g. pre-procedural discontinuation of medication, provocative agent, solution, infusion time, and target artery) and techniques used for measurements (e.g. doppler vs thermodilution technique). CONCLUSIONS This lack of consensus on a uniform functional testing protocol hampers both a broader clinical acceptance of the concepts of coronary vasomotor dysfunction, and the widespread adoption of such testing protocols in current clinical practice. Furthermore, the endotype of coronary vasomotor dysfunction might differ between the few specialised centres that perform coronary vasomotor function testing as a result of the use of different protocols. In this review we provide an overview of the variations in coronary vasomotor function testing used and discuss the practical principles and pitfalls of coronary vasomotor function testing.

Background We examined the link between increased intra-abdominal pressure, intracranial pressure, and vasopressin release as a potential mechanism. Intra-abdominal pressure, produced by abdominal-cavity insufflation with carbon dioxide (CO2) during laparoscopic abdominal procedures to facilitate visualization, is associated with various complications, including arterial hypertension and oliguria. Methods Mean arterial pressure, optic nerve sheath diameter, measured as a proxy for intracranial pressure, plasma vasopressin, serum and urine osmolarity, and urine output were measured 4 times during laparoscopic sleeve gastrectomy in 42 patients: before insufflation with CO2 (T0); after insufflation to 15 cm water (H2O) pressure, with 5 cm H2O positive end-expiratory pressure (T1); after positive end-expiratory pressure was raised to 10 cm H2O (T2); and after a return to the baseline state (T3). Mean values at T0 to T3 and the directional consistency of changes (increase/decrease/ unchanged) were compared among the 4 data-collection points. Results Statistically significant elevations (all P ≤ .001) were noted from T0 to T1 and from T0 to T2 in mean arterial pressure, optic nerve sheath diameter, and vasopressin, followed by decreases at T3. For optic nerve sheath diameter and vasopressin, the increases at T1 and T2 occurred in 98% and 100% of patients, ultimately exceeding normal levels in 88 and 97%, respectively. Conversely, urine output fell from T0 to T1 and T2 by 60.9 and 73.4%, decreasing in 88.1% of patients (all P Conclusion Increased mean arterial pressure, intracranial pressure, and vasopressin release appear to be intermediary steps between increased intra-abdominal pressure and oliguria. Further research is necessary to determine any causative links between these physiological changes.

Context Recent evidence suggests that vasomotor symptoms (VMS) or hot flashes in the postmenopausal reproductive state and polycystic ovary syndrome (PCOS) in the premenopausal reproductive state emanate from the hyperactivity of Kiss1 neurons in the hypothalamic infundibular/arcuate nucleus (KNDy neurons). Objective We demonstrate in 2 murine models simulating menopause and PCOS that a peripherally restricted kappa receptor agonist (PRKA) inhibits hyperactive KNDy neurons (accessible from outside the blood–brain barrier) and impedes their downstream effects. Design Case/control. Setting Academic medical center. Participants Mice. Interventions Administration of peripherally restricted kappa receptor agonists and frequent blood sampling to determine hormone release and body temperature. Main Outcome Measures LH pulse parameters and body temperature. Results First, chronic administration of a PRKA to bilaterally ovariectomized mice with experimentally induced hyperactivity of KNDy neurons reduces the animals’ elevated body temperature, mean plasma LH level, and mean peak LH per pulse. Second, chronic administration of a PRKA to a murine model of PCOS, having elevated plasma testosterone levels and irregular ovarian cycles, suppresses circulating levels of LH and testosterone and restores normal ovarian cyclicity. Conclusion The inhibition of kisspeptin neuronal activity by activation of kappa receptors shows promise as a novel therapeutic approach to treat both VMS and PCOS in humans.

Objective Palpitation, or the sensation of rapid or irregular heartbeats, is common in menopausal women; however, the precise underlying mechanisms are unknown. We aimed to investigate factors associated with palpitation in middle-aged women. Methods Medical records of 394 women aged 40 to 59 years (108 premenopausal, 85 perimenopausal, and 201 postmenopausal) were analyzed cross-sectionally. Palpitation severity was estimated based on responses to the Menopausal Symptom Scale. Effects of background characteristics, including age, menopausal status, body composition, cardiovascular parameters, basal metabolism, physical fitness, lifestyle factors, vasomotor, and psychological symptoms on palpitation were assessed using multivariate logistic regression analysis. The association between autonomic nervous system activity and palpitation was also analyzed in 198 participants. Results Prevalence of palpitation by severity was as follows: none, 26.4%; mild, 32.7%; moderate, 29.4%; severe, 11.4%. In univariate analyses, the more severely the women were affected by palpitation, 1) the higher their systolic blood pressure, 2) the less exercise they performed, 3) the lower they scored in the sit-and-reach test, 4) the higher their vasomotor symptoms score in the Menopausal Health Related-Quality of Life questionnaire, and 5) the higher their Hospital Anxiety and Depression Scale. Multiple logistic regression analysis revealed that moderate to severe palpitation was independently associated with the vasomotor symptom score (adjusted odds ratio [95% confidence interval]: 1.18 [1.07-1.31]) and Hospital Anxiety and Depression Scale anxiety subscale score (1.19 [1.12-1.27]). Conclusions Rapid or irregular heartbeats are highly prevalent in middle-aged women. It is not associated with age, menopausal status, heart rate, arrhythmia, autonomic nervous system activity, caffeine, or alcohol consumption, but with vasomotor symptoms and anxiety.

BACKGROUND/AIM: Coronavirus 2019 disease (Covid-19) was first seen in December 2019 and afterwards it became a pandemic. Several systemic involvements have been reported in Covid-19 patients. In this study, it was aimed to investigate the cerebrovascular hemodynamics in patients with Covid-19. MATERIALS AND METHODS: The sample of this study was conducted on 20 patients hospitalized in our clinic diagnosed with Covid-19 via PCR modality and 20 healthy volunteers of similar age and sex. Bilateral middle cerebral arteries were investigated with Transcranial Doppler Ultrasonography. Basal serebral blood flow velocities and vasomotor reactivity rates were determined and compared as statistically. RESULTS: When patient and control groups were compared, the mean blood flow velocity was found to be higher in Covid-19 patients than the healthy volunteers and it was statistically significant (p = 0.00). The mean vasomotor reactivity rates values were found to be lower in Covid-19 group than the healthy group and also it was statistically significant (p = 0.00). CONCLUSION: An increase in cerebral basal blood velocity and a decrease in vasomotor reactivity rates in patients with Covid-19 can be considered as an indicator of dysfunction of cerebral hemodynamics in central nervous system and this can be evaluated as a result of endothelial dysfunction.

Insufficient sleep is associated with endothelial vasomotor dysfunction and increased cardiovascular risk. Regular aerobic exercise is an effective lifestyle strategy for improving endothelial function and, in turn, reducing cardiovascular risk. We tested the hypotheses that regular aerobic exercise would 1) improve endothelial vasodilation and 2) decrease endothelin (ET)-1-mediated vasoconstrictor tone in middle-aged adults who chronically sleep

This study aimed to find the associations between vasomotor symptoms (VMS) and metabolic syndrome (MetS) in Chinese middle-aged women in a cross-sectional study.A total of 675 participants were recruited from an urban Chinese community. MetS was defined by the 2009 criteria of the Joint Interim Statement. VMS including hot flashes and sweats, blood pressure, weight, height, waist circumference (WC), serum glucose, triglycerides, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), estradiol, and follicle-stimulating hormone (FSH) were collected.The presence of hot flashes was independently associated with the risk of MetS after adjusting for age, menopausal status, FSHWomen with hot flashes had a higher risk of MetS. Both hot flashes and sweats were related to a higher amount of central fat indicated by WC and higher triglycerides, but were not related to blood pressure, glucose, and HDL in Chinese women.

BACKGROUND Emerging evidence indicates that the pancreas serves as a major source of degrading protease activities and that uncontrolled proteolytic receptor cleavage occurs under hypertensive conditions, which leading to systemic dysfunction and end-organic damage. However, changes in pancreatic microcirculation profiles during the progression of hypertension remain unknown. METHODS Pancreatic microcirculatory blood distribution patterns and microvascular vasomotion of spontaneously hypertensive rats (SHRs) and normotensive control Wistar Kyoto rats at 5, 8, 13, and 18 weeks of age were determined. Wavelet transform analysis was performed to convert pancreatic microhemodynamic signals into time–frequency domains and construct 3-dimensional spectral scalograms. The amplitudes of characteristic oscillators including endothelial, neurogenic, myogenic, respiratory, and cardiac oscillators were compared among groups. Plasma nitrite/nitrate levels were measured using a Griess reaction. Additionally, endothelin-1, malondialdehyde, superoxide dismutase, and interleukin-6 levels were determined by enzyme-linked immunosorbent assay. RESULTS SHRs exhibited a reduced blood distribution pattern with progressively decreased average blood perfusion, amplitude, and frequency of microvascular vasomotion. Wavelet transform spectral analysis revealed significantly reduced amplitudes of endothelial oscillators from 8- to 18-week-old SHRs. Additionally, the blood microcirculatory chemistry complements explained the microhemodynamic profiles partially, as demonstrated by an increase in plasma nitrite/nitrate, endothelin-1, malondialdehyde, and interleukin-6 levels and a decreased superoxide dismutase level in SHRs. CONCLUSIONS Pancreatic microcirculation profiles are abnormal in the progression of hypertension in SHRs, including a disarranged blood distribution pattern, impaired microvascular vasomotion, and reduced amplitudes of endothelial oscillators., Graphical Abstract Graphical Abstract

Idiopathic small fiber neuropathy (iSFN) lacks broadly accepted diagnostic criteria, which hinders its timely diagnosis and treatment. A systematic literature review was performed to assess the published screening and diagnostic criteria for iSFN, excluding studies where SFN was of well-established etiology. Eighty-four clinical studies and seven guideline/review publications were included in this systematic review. Substantial heterogeneity existed in iSFN diagnostic criteria. The most common set of criteria to diagnose iSFN [presence of any symptoms of iSFN, absence of large fiber involvement, and reduced intraepidermal nerve fiber density (IENFD)] was used in only 14% of studies. Mandatory individual criteria to confirm iSFN included any sensory symptoms (60% of studies), pain (19% of studies), small fiber signs (20% of studies), absence of large fiber signs (62% of studies), reduced IENFD (38% of studies), and autonomic symptoms (1% of studies). This review highlights a clear need for standardized, evidence-based guidelines for diagnosing iSFN.

Context During the menopausal transition, there is a greater likelihood of the prevalence of various bothersome symptoms, including vasomotor symptoms (VMS) and mood symptoms. Objective To investigate the association among bothersome VMS and symptoms of anxiety and depression in Chinese women during perimenopause and early in menopause. Design, Patients, Setting, and Interventions This study included 430 midlife Chinese women who had experienced natural menopause and were followed up for 10 years. A structured questionnaire was provided annually, comprising the VMS Bother Score (range 1-8) from the Menopause-Specific Quality of Life questionnaire, the Hospital Anxiety and Depression Scale, and other physical and behavioral factors. Results Among the 430 women evaluated, 78.8% had experienced VMS during long-term follow-up. The overall level of VMS bother score was relatively low (1.92 ± 1.32). Both anxiety and depressive symptoms were significantly associated with VMS bother. After adjusting for potential covariates, the association between anxiety or depression symptoms and VMS bother remained highly significant. Menopausal stage, body mass index, general health, follicle-stimulating hormone, and estradiol were independent contributors to VMS. In time-lagged (1-year) models, VMS bother scores significantly predicted the risk of symptoms of both anxiety and depression the following year. In contrast, anxiety symptoms, rather than depressive symptoms, could predict VMS bother the following year. Conclusion The prevalence of VMS in our cohort was higher than has been previously reported; however, the overall level of bother was relatively low. This study demonstrated a strong relationship between VMS bother and mood symptoms in Chinese women progressing from perimenopause through natural menopause.

Introduction: The second-line treatment of endometriosis-related pain symptoms includes injectable depot formulations of gonadotropin-releasing hormone analogs (GnRH-as). These drugs improve the symptomatology by inducing a hypoestrogenic status and a consequent regression of endometriotic implants. However, GnRH-a may cause a not negligible rate of adverse events, in particular vasomotor symptoms and bone mineral density loss, that may limit patients’ adherence and safety on long-term treatment. Several strategies have been suggested to improve the compliance to treatment. Areas covered: This narrative review aims to give an overview of the safety and tolerability of GnRH-a therapy and to present the different options of steroidal and non-steroidal add-back therapies in order to reduce the hypoestrogenic side effects. Expert opinion: Side effects of long term GnRH-a treatment are particularly relevant. Although it has been known the efficacy of GnRH-as for treating endometriosis-associated pain, the best schedules of therapy in terms of duration and dosages are still to be defined. The ideal treatment schedule of GnRH-a is still a matter of debate as to the optimal add-back combination.

Aging leads to a loss of vasomotor control. Both vasodilation and vasoconstriction are affected. Decreased nitric oxide&ndash, cGMP-mediated relaxation is a hallmark of aging. It contributes to vascular disease, notably hypertension, infarction, and dementia. Decreased vasodilation can be caused by aging independently from cardiovascular risk factors. This process that can be mimicked in mice in an accelerated way by activation of the DNA damage response. Genetic deletion of the DNA repair enzyme ERCC1 endonuclease in mice, as in the case of Ercc1&Delta, /- mice, can be used as a tool to accelerate aging. Ercc1&Delta, /- mice develop age-dependent vasomotor dysfunction from two months after birth. In the present study we tested if chronic treatment with sildenafil, a phosphodiesterase 5 inhibitor that augments NO&ndash, cGMP signaling, can reduce the development of vasomotor dysfunction in Ercc1&Delta, /- mice. Ercc1&Delta, /- mice and wild-type littermates were treated with 10 mg/kg/d of sildenafil from the age of 6 to the age of 14 weeks. Blood pressure and in vivo and ex vivo vasomotor responses were measured at the end of the treatment period. Ercc1&Delta, /- mice developed decreased reactive hyperemia, and diminished NO&ndash, cGMP-dependent acetylcholine responses. The diminished acetylcholine response involved both endothelial and vascular smooth muscle cell signaling. Chronic sildenafil exclusively improved NO&ndash, cGMP signaling in VSMC, and had no effect on endothelium-derived hyperpolarization. Sildenafil also improved KCl hypocontractility in Ercc1&Delta, /- mice. All effects were blood pressure-independent. The findings might be of clinical importance for prevention of morbidities related to vascular aging as well as for progeria patients with a high risk of cardiovascular disease.

NEW FINDINGS: What is the central question of this study? Does chronic mountain sickness (CMS) alter sympathetic neural control and arterial baroreflex regulation of blood pressure in Andean (Quechua) highlanders? What is the main finding and its importance? Compared to healthy Andean highlanders, basal sympathetic vasomotor outflow is lower, baroreflex control of muscle sympathetic nerve activity is similar, supine heart rate is lower and cardiovagal baroreflex gain is greater in mild CMS. Taken together, these findings reflect flexibility in integrative regulation of blood pressure that may be important when blood viscosity and blood volume are elevated in CMS. ABSTRACT: The high-altitude maladaptation syndrome chronic mountain sickness (CMS) is characterized by excessive erythrocytosis and frequently accompanied by accentuated arterial hypoxaemia. Whether altered autonomic cardiovascular regulation is apparent in CMS is unclear. Therefore, during the 2018 Global REACH expedition to Cerro de Pasco, Peru (4383 m), we assessed integrative control of blood pressure (BP) and determined basal sympathetic vasomotor outflow and arterial baroreflex function in eight Andean natives with CMS ([Hb] 22.6 ± 0.9 g·dL(-1) ) and seven healthy highlanders ([Hb] 19.3 ± 0.8 g·dL(-1) ). R-R interval (RRI, electrocardiogram), beat-by-beat BP (photoplethysmography) and muscle sympathetic nerve activity (MSNA; microneurography) were recorded at rest and during pharmacologically induced changes in BP (modified Oxford test). Although [Hb] and blood viscosity (7.8 ± 0.7 vs. 6.6 ± 0.7 cP; d = 1.7, P = 0.01) were elevated in CMS compared to healthy highlanders, cardiac output, total peripheral resistance and mean BP were similar between groups. The vascular sympathetic baroreflex MSNA set-point (i.e. MSNA burst incidence) and reflex gain (i.e. responsiveness) were also similar between groups (MSNA set-point, d = 0.75, P = 0.16; gain, d = 0.2, P = 0.69). In contrast, in CMS the cardiovagal baroreflex operated around a longer RRI (960 ± 159 vs. 817 ± 50 ms; d = 1.4, P = 0.04) with a greater reflex gain (17.2 ± 6.8 vs. 8.8 ± 2.6 ms·mmHg(-1) ; d = 1.8, P = 0.01) versus healthy highlanders. Basal sympathetic vasomotor activity was also lower compared to healthy highlanders (33 ± 11 vs. 45 ± 13 bursts·min(-1) ; d = 1.0, P = 0.08). In conclusion, our findings indicate adaptive differences in basal sympathetic vasomotor activity and heart rate compensate for the haemodynamic consequences of excessive erythrocyte volume and contribute to integrative blood pressure regulation in Andean highlanders with mild CMS.

Objective: Vasomotor symptoms (hot flashes, night sweats) are common during the menopausal transition. Pharmacotherapy is effective but is associated with health risks for some women. There is an increasing demand for non-pharmacological interventions. The CBT-Meno protocol is a psychological intervention targeting a range of common menopausal symptoms. We compared the impact of CBT-Meno vs. waitlist on objective and subjective measures of vasomotor symptoms and on the relationship between vasomotor symptoms and sleep difficulties.Materials: The participants were 36 perimenopausal or postmenopausal women with co-occurring depressive symptoms who participated in the CBT-Meno trial (clinicaltrials.gov NCT02480192). Subjective measures included the Hot Flash Related Daily Interference Scale, the Greene Climacteric Scale, and the Pittsburgh Sleep Quality Inventory. Objective (physiological) and 'in-the-moment' measures of vasomotor symptoms were assessed with sternal skin conductance.Results: Greater improvements in vasomotor 'bothersomeness' and 'interference' were observed in the CBT-Meno condition compared to the waitlist condition. No between-group differences were observed in vasomotor frequency (subjectively or objectively recorded) or severity ratings. Sleep disturbance was unrelated to objectively measured vasomotor symptom frequency.Conclusion: The CBT-Meno trial improved subjective but not objective (physiological) measures of vasomotor symptoms. Self-reported sleep difficulties were unrelated to subjective or objective vasomotor symptoms.

Purpose The hallmark menopausal symptom, vasomotor symptoms (VMS), has been linked to adverse health indicators. However, the relationship between VMS and biological aging has not been tested. We examined associations between menopausal VMS and biological aging as assessed by 2 DNA methylation-based epigenetic aging indicators previously linked to poor health outcomes. Methods Participants were members of the Women’s Health Initiative Observational Study integrative genomics substudy (N = 1206) who had both ovaries and were not taking hormone therapy. Relationships between VMS at enrollment (presence, severity) or VMS timing groups (no VMS: not at menopause onset nor at study enrollment; early VMS: at menopause onset but not at enrollment; persistent VMS: at menopause onset and study enrollment; and late VMS: at enrollment but not at menopause onset) and epigenetic clock indicators predictive of physical aging and early death (DNAm PhenoAge, DNAm GrimAge) were tested in linear regression models adjusting for age, race/ethnicity, hysterectomy, education, body mass index, smoking, and, in additional models, sleep disturbance. Results Women were on average 65 years of age at enrollment. Severe hot flashes at enrollment were associated with higher DNAm PhenoAge [relative to no hot flashes: B (SE) = 2.79 (1.27), P = 0.028, multivariable]. Further, late-occurring VMS were associated with both higher DNAm PhenoAge [B (SE) = 2.15 (0.84), P = 0.011] and DNAm GrimAge [B (SE) = 1.09 (0.42), P = 0.010, multivariable] relative to no VMS. Main Conclusions Among postmenopausal women, severe or late-occurring VMS were associated with accelerated epigenetic age, controlling for chronological age. Postmenopausal women with severe or late-occurring VMS may have greater underlying epigenetic aging.

It has become clear that sodium glucose cotransporter (SGLT)-2 inhibitors not only do not increase the incidence of cardiovascular events but they also reduce the duration of hospitalization for heart failure in type 2 diabetes mellitus (T2DM) patients. The administration of SGLT2 inhibitor in T2DM patients with hypertension and a fluid retention tendency lowers the blood pressure and mitigates fluid retention. It also reduces the heart rate in T2DM patients with a fast heart rate. As an explanation for the multifaceted effects of SGLT2 inhibitors on hemodynamics, we hypothesize that these agents act on the inter-organ communication pathway, which modulates the sympathetic nerve activity to the cardiovascular system.

Objectives Cardiopulmonary bypass-induced endothelial dysfunction has been inferred by changes in pulmonary vascular resistance, alterations in circulating biomarkers, and postoperative capillary leak. Endothelial-dependent vasomotor dysfunction of the systemic vasculature has never been quantified in this setting. The objective of the present study was to quantify acute effects of cardiopulmonary bypass on endothelial vasomotor control and attempt to correlate these effects with postoperative cytokines, tissue edema, and clinical outcomes in infants. Design Single-center prospective observational cohort pilot study. Setting Pediatric cardiac ICU at a tertiary children's hospital. Patients Children less than 1 year old requiring cardiopulmonary bypass for repair of a congenital heart lesion. Intervention None. Measurements and main results Laser Doppler perfusion monitoring was coupled with local iontophoresis of acetylcholine (endothelium-dependent vasodilator) or sodium nitroprusside (endothelium-independent vasodilator) to quantify endothelial-dependent vasomotor function in the cutaneous microcirculation. Measurements were obtained preoperatively, 2-4 hours, and 24 hours after separation from cardiopulmonary bypass. Fifteen patients completed all laser Doppler perfusion monitor (Perimed, Jarfalla, Sweden) measurements. Comparing prebypass with 2-4 hours postbypass responses, there was a decrease in both peak perfusion (p = 0.0006) and area under the dose-response curve (p = 0.005) following acetylcholine, but no change in responses to sodium nitroprusside. Twenty-four hours after bypass responsiveness to acetylcholine improved, but typically remained depressed from baseline. Conserved endothelial function was associated with higher urine output during the first 48 postoperative hours (R = 0.43; p = 0.008). Conclusions Cutaneous endothelial dysfunction is present in infants immediately following cardiopulmonary bypass and recovers significantly in some patients within 24 hours postoperatively. Confirmation of an association between persistent endothelial-dependent vasomotor dysfunction and decreased urine output could have important clinical implications. Ongoing research will explore the pattern of endothelial-dependent vasomotor dysfunction after cardiopulmonary bypass and its relationship with biochemical markers of inflammation and clinical outcomes.

Isocapnic hyperoxia (IH) evokes cerebral and peripheral hypoperfusion via both disturbance of redox homeostasis and reduction in nitric oxide (NO) bioavailability. However, it is not clear whether the magnitude of the vasomotor responses depends on the vessel network exposed to IH. To test the hypothesis that the magnitude of IH-induced reduction in peripheral blood flow (BF) may differ from the hypoperfusion response observed in the cerebral vascular network under oxygen-enriched conditions, nine healthy men (25 ± 3 yr, mean ± SD) underwent 10 min of IH during either saline or vitamin C (3 g) infusion, separately. Femoral artery (FA), internal carotid artery (ICA), and vertebral artery (VA) BF (Doppler ultrasound), as well as arterial oxidant (8-isoprostane), antioxidant [ascorbic acid (AA)], and NO bioavailability (nitrite) markers were simultaneously measured. IH increased 8-isoprostane levels and reduced nitrite levels; these responses were followed by a reduction in both FA BF and ICA BF, whereas VA BF did not change. Absolute and relative reductions in FA BF were greater than IH-induced changes in ICA and VA perfusion. Vitamin C infusion increased arterial AA levels and abolished the IH-induced increase in 8-isoprostane levels and reduction in nitrite levels. Whereas ICA and VA BF did not change during the vitamin C-IH trial, FA perfusion increased and reached similar levels to those observed during normoxia with saline infusion. Therefore, the magnitude of IH-induced reduction in femoral blood flow is greater than that observed in the vessel network of the brain, which might involve the determinant contribution that NO has in the regulation of peripheral vascular perfusion.

Background: The use of poly- l -lactide acid-based bioresorbable scaffolds is limited in daily clinical practice because of safety concerns and lack of physiological benefit. Magnesium-based bioresorbable scaffold (MgBRS) presents a short resorption period ( Methods: This investigator-driven, multicenter, randomized, single-blind, controlled trial randomized ST-segment–elevation myocardial infarction patients 1:1 to SES or MgBRS at 11 academic centers. The primary end point was the rate of increase (≥3%) after nitroglycerin in mean lumen diameter of the in-stent/scaffold segment at 12 months with superiority of MgBRS over SES in the as-treated population. The main secondary end points included angiographic parameters of restenosis, device-oriented composite end point, their individual components, and device thrombosis rate. Besides, endothelial-dependent vasomotor response to acetylcholine (ie, endothelial function) was also assessed in a subgroup of patients (n=69). Results: Between June 2017 and June 2018, 150 ST-segment–elevation myocardial infarction patients were randomized (MgBRS, n=74; SES, n=76). At 1 year, the primary end point was significantly higher in the MgBRS arm (56.5% versus 33.8%; P =0.010). Conversely, late lumen loss was significantly lower in the SES group (in-segment: 0.39±0.49mm versus 0.02±0.27mm, P P P =0.030). Definite thrombosis rate was similar between groups (1[1.4%] in the MgBRS arm versus 2[2.6%] in the SES group; P =1.0). Endothelial function assessment at device segment evidenced a more pronounced vasoconstrictive response to maximal dose of acetylcholine in the MgBRS arm (−8.3±3.5% versus −2.4±1.3% in the SES group, P =0.003). Conclusions: When compared to SES, MgBRS demonstrated a higher capacity of vasomotor response to pharmacological agents (either endothelium-independent or endothelium-dependent) at 1 year. However, MgBRS was associated with a lower angiographic efficacy, a higher rate of target lesion revascularization, without thrombotic safety concerns. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03234348.

Background There is substantial variation in how menopausal vasomotor symptoms are reported and measured among intervention studies. This has prevented meaningful comparisons between treatments and limited data synthesis. Objectives To review systematically the outcome reporting and measures used to assess menopausal vasomotor symptoms from randomised controlled trials of treatments. Search strategy We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from inception to May 2018. Selection criteria Randomised controlled trials with a primary outcome of menopausal vasomotor symptoms in women and a sample size of at least 20 women per study arm. Data collection and analysis Data about study characteristics, primary vasomotor-related outcomes and methods of measuring them. Main results The search identified 5591 studies, 214 of which were included. Forty-nine different primary reported outcomes were identified for vasomotor symptoms and 16 different tools had been used to measure these outcomes. The most commonly reported outcomes were frequency (97/214), severity (116/214), and intensity (28/114) of vasomotor symptoms or a composite of these outcomes (68/214). There was little consistency in how the frequency and severity/intensity of vasomotor symptoms were defined. Conclusions There is substantial variation in how menopausal vasomotor symptoms have been reported and measured in treatment trials. Future studies should include standardised outcome measures which reflect the priorities of patients, clinicians, and researchers. This is most effectively achieved through the development of a Core Outcome Set. This systematic review is the first step towards development of a Core Outcome Set for menopausal vasomotor symptoms. Tweetable summary Menopausal hot flushes and night sweats have been reported in 49 different ways in clinical research. A core outcome set is urgently required.

Objective Vasomotor symptoms (VMS) have been consistently reported as the leading predictor of health-related quality of life (HRQOL) among menopausal women, and the strongest indication for treatment. The North American Menopause Society endorses the use of oral estrogen for the treatment of VMS based on a Cochrane meta-analysis. The Cochrane review concludes that oral hormone therapy reduces the frequency and severity of VMS. The objective of this review is to critically appraise the outcome measures used in these clinical trials to evaluate whether there is adequate evidence that oral hormone therapy improves HRQOL. Methods Each trial in the 2004 Cochrane review of oral hormone therapy for the management of VMS was evaluated with respect to study design, outcome measures, and method of analysis. Results Twenty-four randomized, double-blind, placebo-controlled clinical trials were appraised. Six trials were excluded from the Cochrane meta-analysis due to inadequate reporting of outcome measures. Of the remaining trials, 15 trials assessed only symptom frequency and/or severity. One trial used a subscale of the General Health Questionnaire. Two trials used the Greene Climacteric Scale, a validated outcome measure in menopausal women, to directly assess the impact of hormone therapy on HRQOL. Both studies showed an improvement in HRQOL in the hormone-treated group, although the sample size was small (n = 118) and the effect was modest. Conclusion Although oral hormone therapy improves VMS scores, there is a paucity of evidence on whether it improves HRQOL in menopausal women. Future studies using validated, patient-reported outcome measures that directly assess HRQOL are needed.

BACKGROUND Hypertension usually accompanies the elevated sympathetic activity and sleep interruption. Few researches explored the dynamic changes and possible correlations in cardiovascular functions and sleep patterns during the development of hypertension. In contrast, exercise training provides several benefits on cardiovascular and sleep function in hypertensive subjects. However, controlling various factors during a long period of exercise training is difficult in hypertensive subjects, an animal model may be essential. This study aimed to explore dynamic changes in cardiovascular functions and sleep patterns during the development period of hypertension (10–20 weeks old) in spontaneously hypertensive rats (SHRs) and effects of exercise intervention. METHODS We used the treadmill exercise model for 8 weeks and started when SHRs were 12 weeks old. Electroencephalogram, electromyogram, electrocardiogram, and blood pressure (BP) were recorded simultaneously for 24 hours once a week over 11 weeks. RESULTS Untrained SHRs revealed the age-related increments in BP, and the significant increasing slopes of differences on BP and vascular sympathetic activity were observed during the development period of hypertension. Compared with untrained rats, age-related increases in BP and vascular sympathetic activity were significantly suppressed in trained SHRs. Nevertheless, trained SHRs showed more quiet sleep time at partial weeks. The positive correlation between the differences from 10 weeks of vascular sympathetic activity and BP was disappeared in trained SHRs. CONCLUSIONS There existed the significant correlation between the dynamic changes of vascular sympathetic activity and age-related elevation of BP during the development period of hypertension; however, exercise prevented hypertension and disrupted this correlation.

Vasomotor symptoms (VMSs) are the most common symptoms affecting women during the menopause. Besides, affective symptoms may share with VMS a common biological pathophysiology. The current multicenter quantitative research was based on an online survey aimed to evaluate the impact of VMS in peri- and post-menopausal Italian women and to identify the main barriers to seeking help. The most frequent bothersome VMSs were hot flashes (41%), night sweats (31%), and over-heating (31%). Almost 87% of women experienced three or more simultaneous symptoms. Emotions verbalized by women indicate how intensely hot flushes and neuro-vegetative symptoms impact life: embarrassment, confusion, depression, impact on social/personal relationships, and guiltiness. Up to 43% of all women suffering from VMS were not treating the symptoms. Although 92% of women reported prior knowledge of the VMS condition, only 12% do something about it straight away after the appearance of VMS. This survey provided real-life observational data from a large population of peri-menopausal women and highlighted the important impact of VMS, its neurovegetative comorbidities and its significant burden effect on social life. Physicians must be more adaptive and inquisitive to evaluate and detect incipient VMS, as this will indicate the vulnerability to severe symptomatology and pathological brain aging.

Aims The recent identification of acid sensing ion channels (ASICs) in vascular beds suggests their possible involvement in modulating vasomotor tone. Therefore, we investigated the gene expression profiles of ASIC subtypes in the middle cerebral artery (MCA) of Wistar rats and the functional implication of ASICs in acidosis-induced relaxation as well as maintenance of resting tension. Main methods Real time PCR was employed to study the pattern of ASIC mRNA expression in the MCA wall in comparison with (i) matching brain tissue samples and (ii) arteries cultured for 24 h and 48 h. The functional implication regarding vasomotor response to acidosis and maintenance of resting tension was assessed using in vitro myography. Key findings A robust mRNA expression of ASIC-1, -2 and -4 was found in brain tissue samples and to a lower extent in freshly isolated MCA. In the MCA wall, short term culture induced a down-regulation of ASIC-1 and -2 expression without any remarkable change in ASIC-4 expression. Acidosis induced a pH-related relaxation of freshly isolated MCA ring segments, being more pronounced after short term culture. Incubation with the ASIC blocker amiloride moderately enhanced acidosis-induced relaxation, in cultured MCAs somewhat stronger than in freshly isolated vessels. In addition, amiloride resulted in a decrease of resting tension, albeit only in freshly isolated MCA. Significance Our results comprehensively describe ASIC subtype composition in the rat MCA in physiological and pathological conditions and strongly suggest the involvement of ASICs in the modulation of vasomotor responses under conditions of normal or decreased pH values.

The acute blood pressure (BP) decrease is greater after evening than morning exercise, suggesting that evening training (ET) may have a greater hypotensive effect.This study aimed to compare the hypotensive effect of aerobic training performed in the morning versus evening in treated hypertensives.Fifty treated hypertensive men were randomly allocated to three groups: morning training (MT), ET, and control (C). Training groups cycled for 45 min at moderate intensity (progressing from the heart rate of the anaerobic threshold to 10% below the heart rate of the respiratory compensation point), while C stretched for 30 min. Interventions were conducted 3 times per week for 10 wk. Clinic and ambulatory BP and hemodynamic and autonomic mechanisms were evaluated before and after the interventions. Clinic assessments were performed in the morning (7:00-9:00 AM) and evening (6:00-8:00 PM). Between-within ANOVA was used (P ≤ 0.05).Only ET decreased clinic systolic BP differently from C and MT (morning assessment -5 ± 6 mm Hg and evening assessment -8 ± 7 mm Hg, P0.05). Only ET reduced 24 h and asleep diastolic BP differently from C and MT (-3 ± 5 and -3 ± 4 mm Hg, respectively, P0.05). Systemic vascular resistance decreased from C only in ET (P = 0.03). Vasomotor sympathetic modulation decreased (P = 0.001) and baroreflex sensitivity (P0.02) increased from C in both training groups with greater changes in ET than MT.In treated hypertensive men, aerobic training performed in the evening decreased clinic and ambulatory BP due to reductions in systemic vascular resistance and vasomotor sympathetic modulation. Aerobic training conducted at both times of day increases baroreflex sensitivity, but with greater after ET.

(1) Background: Traumatic brain injury (TBI) frequently occurs worldwide, resulting in high morbidity and mortality. Here, we hypothesized that TBI impairs an autoregulatory mechanism, namely the flow-induced constriction of isolated rat middle cerebral arteries (MCAs). (2) Methods: TBI was induced in anaesthetized rats by weight drop model, and then MCAs were isolated and transferred into a pressure-flow chamber. The internal diameter was measured by a video-microscopy. (3) Results: In MCAs from intact rats, increases in flow and pressure + flow elicited constrictions (−26 ± 1.9 µm and −52 ± 2.8 µm, p &lt, 0.05), which were significantly reduced after TBI or in the presence of thromboxane-prostanoid (TP receptor) antagonist SQ 29,548. Flow-induced constrictions were significantly reduced by HET0016, inhibitor of cytochrome P450 4A (CYP450 4A). Arachidonic acid, (AA, 10−7 M), and CYP-450 4A metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) elicited constrictions of intact MCA (−26 ± 2.3% and −31 ± 3.6%), which were significantly reduced after TBI (to 11 ± 1.3% and −16 ±2.5%). The TP receptor agonist U46619 (10−7 M) elicited substantial constrictions of MCA from intact rats (−21 ± 3.3%), which were also significantly reduced, after TBI (to −16 ± 2.4%). (4) Conclusions: Flow-induced constrictor response of MCA is impaired by traumatic brain injury, likely due to the reduced ability of cytochrome P450 4A to convert arachidonic acid to constrictor prostaglandins and the mitigated sensitivity of thromboxane-prostanoid receptors.

Objective - We have previously shown that epithelial ovarian cancer (EOC) and its treatments have negative effects on long-term quality of life (QoL) and fatigue. The present multicenter study investigated the main menopausal symptoms and gynecological management of EOC survivors (EOCS). Methods - 166 patients with relapse-free ≥3 years after the end of treatment attended a consultation with a gynecologist, including a questionnaire related to vasomotor symptoms (VMS) and sexuality, a clinical examination, a blood sample and an osteodensitometry. QoL, fatigue, insomnia and mood disorders were measured with validated questionnaires and correlated to VMS. VMS and QoL were assessed according to natural menopause (NM) or surgical menopause (SM). Results - Mean age at the survey was 62 [21–83] years and stage III/IV (48%). Mean delay since the end of treatment was 6 years. Fifty-nine patients (36%) had SM. Half of patients reported VMS. Seventy-two percent of EOCS with SM had VMS compared to 41% with NM (P < .001). VMS were not associated with poor global QoL, fatigue, insomnia or mood disorders. Two-thirds of EOCS reported a decrease in libido. Patients with SM showed a greater decrease in libido than NM (P < .02). Fourteen percent of them had osteoporosis and 50% osteopenia. Among the 85 patients with VMS, 80 did not receive HRT after cancer treatment. At the time of the survey, only 7 (4%) patients were receiving hormone replacement therapy (HRT). Conclusions - VMS and sexual disorders are frequently reported by EOCS, particularly among patients with SM. Most EOCS with menopausal symptoms could benefit from HRT to improve these symptoms.

This study investigated the cardiac, vasomotor, and myocardial branches of the baroreflex in fibromyalgia using the spontaneous sequence method. Systolic blood pressure (SBP), interbeat interval (IBI), stroke volume (SV), pre-ejection period (PEP), and total peripheral resistance (TPR) were continuously recorded in 40 fibromyalgia patients and 30 healthy individuals during a cold pressor test and a mental arithmetic task. Sequences of covariation between SBP and IBI (cardiac branch), SV and PEP (myocardial branch), and TPR (vasomotor branch) were identified. Baroreflex sensitivity (BRS) was represented by the slope of the regression line between values in the sequences; baroreflex effectiveness (BEI) was indexed by the proportion of progressive SBP changes that elicited reflex responses. Patients exhibited lower BRS in the three branches, lower BEI in the cardiac and vasomotor branches, and reduced reactivity in cardiac BRS and BEI, SBP, IBI, SV, and PEP. Moreover, BRS and BEI were inversely related to clinical pain, cold pressor pain, depression, trait anxiety, sleep problems, and fatigue. Reduced function of the three baroreflex branches implies diminished resources for autonomic inotropic, chronotropic, and vascular regulation in fibromyalgia. Blunted stress reactivity indicates a limited capacity for autonomic cardiovascular adjustment to situational requirements. The associations of BRS and BEI with pain perception may reflect the antinociceptive effects arising from baroreceptor afferents, where reduced baroreflex function may contribute to the hyperalgesia characterizing fibromyalgia. The associations with affective impairments, sleep problems, and fatigue suggest that baroreflex dysfunctions are also involved in the secondary symptoms of the disorder.

Background Cardiovascular disease (CVD) in women has unique features, including associations with reproductive factors that are incompletely understood. Vasomotor symptoms (VMS), the classic menopausal symptom, are linked to CVD risk factors and subclinical CVD. Evidence linking VMS to CVD events is limited. We tested whether frequent and/or persistent VMS were associated with increased risk for fatal and nonfatal CVD events in SWAN (Study of Women’s Health Across the Nation). Methods and Results A total of 3083 women, aged 42 to 52 years at baseline, underwent up to 16 in‐person visits over 22 years. Assessments included questionnaires on VMS frequency (0, 1–5, or ≥6 days/2 weeks), physical measures, phlebotomy, and reported CVD events (myocardial infarction, stroke, heart failure, and revascularization). A subset of events was adjudicated via medical record. Death certificates were obtained. Relationships between baseline VMS or persistent VMS over the follow‐up (proportion of visits with frequent VMS) with combined incident nonfatal and fatal CVD were tested in Cox proportional hazards models adjusted for demographics, medication use, and CVD risk factors. Participants experienced 231 CVD events over the follow‐up. Women with frequent baseline VMS had an elevated risk of subsequent CVD events (relative to no VMS; ≥6 days: hazard ratio [HR] [95% CI], 1.51 [1.05–2.17], P =0.03; 1–5 days: HR [95% CI], 1.02 [0.75–1.39], P =0.89, multivariable). Women with frequent VMS that persisted over time also had an increased CVD event risk (>33% versus ≤33% of visits: HR [95% CI], 1.77 [1.33–2.35], P Conclusions Frequent and persistent VMS were associated with increased risk of later CVD events. VMS may represent a novel female‐specific CVD risk factor.

Chlorisondamine (CSD) has been used to assess the neurogenic contribution to blood pressure (BP) and vasomotor sympathetic tone in animal models. It is assumed that the reduction in BP following CSD administration is associated to decreases in cardiac output (CO) and peripheral resistance, reflecting cardiac and vasomotor sympathetic tone, respectively. Surprisingly, this has not been characterized experimentally in mice, despite the extensive use of this animal model in cardiovascular research. We hypothesize that a specific dose of CSD can selectively block the sympathetic vasomotor tone. To test this hypothesis, we evaluated the effects of different doses of CSD (intraperitoneal) on BP and heart rate (HR) using telemetry, and on CO using echocardiography. BP and HR in normotensive C57Bl/6J mice reduced to a similar extent by all CSD doses tested (1–6 mg/kg). CSD at 6 mg/kg also reduced CO without affecting left ventricular stroke volume or fractional shortening. On the other hand, lower doses of CSD (1 and 2 mg/kg) produced significantly larger BP and HR reductions in DOCA‐salt–induced hypertensive mice, indicating a greater neurogenic BP response. In addition, all doses of CSD reduced CO in hypertensive mice. Our data suggest that the BP response to CSD in mice likely reflects reduced CO and vasomotor sympathetic tone. We conclude that CSD can be used to assess the neurogenic contribution to BP in mice but may not be appropriate for specifically estimating vasomotor sympathetic tone., Ganglionic blocker, chlorisondamine, can be used to assess the neurogenic contribution to BP in mice, but may not be appropriate to specifically estimate the vasomotor sympathetic tone.

Context Menopause, the permanent cessation of menses, reflects oocyte depletion and loss of gonadal steroids. It is preceded by a transition state, the perimenopause, which is characterized by the gradual loss of oocytes, altered responsiveness to gonadal steroid feedback, wide hormonal fluctuations, and irregular menstrual patterns. The goal of this mini-review is to discuss the basic pathophysiology of the menopausal transition and the hormonal and nonhormonal management of clinicopathology attributed to it. Evidence Acquisition A Medline search of epidemiologic, population-based studies, and studies of reproductive physiology was conducted. A total of 758 publications were screened. Evidence Synthesis The reproductive hormonal milieu of the menopausal transition precipitates bothersome vasomotor symptoms, mood disruption, temporary cognitive dysfunction, genitourinary symptoms, and other disease processes that reduce the quality of life of affected women. The endocrine tumult of the menopause transition also exposes racial and socioeconomic disparities in the onset, severity, and frequency of symptoms. Hormone therapy (HT) treatment can be effective for perimenopausal symptoms but its use has been stymied by concerns about health risks observed in postmenopausal HT users who are older than 60 and/or women who have been postmenopausal for greater than 10 years. Conclusions The menopause transition is a disruptive process that can last for over a decade and causes symptoms in a majority of women. It is important for clinicians to recognize early signs and symptoms of the transition and be prepared to offer treatment to mitigate these symptoms. Many safe and effective options, including HT, are available.

Elevated sympathetic vasomotor tone seen in heart failure (HF) may involve dysfunction of the hypothalamic paraventricular nucleus neurons that project to the rostral ventrolateral medulla (PVN-RVLM neurons). This study aimed to elucidate the role of PVN-RVLM neurons in the maintenance of resting renal sympathetic nerve activity (RSNA) after myocardial infarction (MI). In male rats, the left coronary artery was chronically ligated to induce MI. The rats received PVN microinjections of an adeno-associated viral (AAV) vector encoding archaerhodopsin T (ArchT) with the reporter yellow fluorescence protein (eYFP). The ArchT rats had abundant distributions of eYFP-labeled, PVN-derived axons in the RVLM. In anesthetized ArchT rats with MI (n = 12), optogenetic inhibition of the PVN-RVLM pathway achieved by 532-nm-wavelength laser illumination to the RVLM significantly decreased RSNA. This effect was not found in sham-operated ArchT rats (n = 6). Other rat groups received RVLM microinjections of a retrograde AAV vector encoding the red light-drivable halorhodopsin Jaws (Jaws) with the reporter green fluorescence protein (GFP) and showed expression of GFP-labeled cell bodies and dendrites in the PVN. Laser illumination of the PVN at a 635 nm wavelength elicited significant renal sympathoinhibition in Jaws rats with MI (n = 9) but not in sham-operated Jaws rats (n = 8). These results indicate that sympathoexcitatory input from PVN-RVLM neurons is enhanced after MI, suggesting that this monosynaptic pathway is part of the central nervous system circuitry that plays a critical role in generating an elevated sympathetic vasomotor tone commonly seen with HF.NEW & NOTEWORTHY Using optogenetics in rats, we report that sympathoexcitatory input from hypothalamic paraventricular nucleus neurons that project to the rostral ventrolateral medulla is enhanced after myocardial infarction. It is suggested that this monosynaptic pathway makes up a key part of central nervous system circuitry underlying sympathetic hyperactivation commonly seen in heart failure.

Vasomotor symptoms (hot flushes and/or night sweats) affect approximately 80% of women over the menopause transition and can affect quality of life, productivity, and relationships. Vasomotor symptoms are the main reason for seeking treatment during the menopausal transition. Although menopausal hormone therapy (MHT) is effective for symptom management, the majority of symptomatic women do not take MHT. In this article, we review the evidence for non-hormonal treatments for vasomotor symptoms, including pharmacological and non-pharmacological approaches, and provide a clinical algorithm for managing symptomatic women.

We investigated a central antihypertensive effect of acupuncture in rostral ventrolateral medulla (RVLM) in spontaneously hypertensive rats (SHRs). In total, 56 rats were randomly divided into seven groups as follows: the SHR group, SHR+acupuncture (SHR+Acu) group, SHR+nonacupuncture (SHR+Non-acu) group, GW9662+acupuncture (GW9662+Acu) group, GW9662+GW1929 group, GW9662 group, and 2% DMSO group (n = 8 per group). The whole eight Wistar-Kyoto rats were assigned to the WKY group. The acupuncture treatment lasting for 14 days was performed at the Taichong acupoint (LR3) or at a nonacupoint (non-acu) once daily. The peroxisome proliferator-activated receptor (PPAR)-γ agonist GW1929 and the PPAR-γ inhibitor GW9662 were microinjected by the brain stereotactic technique. Blood pressure was measured by the tail-cuff method. Sympathetic vasomotor activity was determined by implanting in a telemetry electrocardiogram radio transmitter. The expression of PPARs in the RVLM of the rats was detected using Western blot. We demonstrated that acupuncture attenuated blood pressure, heart rate, and sympathetic vasomotor activity in SHRs. The protein expression of PPAR-γ was significantly increased in SHRs treated with acupuncture. The antihypertensive effects of acupuncture in SHRs were abrogated by microinjection bilaterally into RVLM of GW9662. Microinjection of GW1929 mimicked the antihypertensive effect of acupuncture. PPAR-γ expression was negatively correlated with blood pressure and sympathetic vasomotor activity in SHRs treated with acupuncture. These results suggested that acupuncture promoted a central antihypertensive effect by increasing the expression of PPAR-γ in RVLM of SHRs.

Leptomeningeal anastomoses (LMAs) are pial collaterals that perfuse the penumbra and important for stroke outcome. We previously showed LMAs from SHRs (spontaneously hypertensive rats) were vasoconstricted compared with normotensive Wistar rats. Here, we investigated mechanisms by which hypertension causes LMA vasoconstriction. SHRs were treated with the ACE (angiotensin-converting enzyme) inhibitor captopril, an Ang II (angiotensin II)–independent antihypertensive agent hydralazine, or vehicle for 5 weeks in drinking water (n=8/group). A group of Wistar rats (n=8) had regular drinking water served as controls. Blood pressure was measured twice weekly by tail-cuff. LMAs were isolated and studied under pressurized conditions. Vasoreactivity of LMAs, including myogenic responses, reactivity to Rho-kinase inhibitor Y-27632, and nitric oxide were measured. Both captopril and hydralazine lowered blood pressure in SHRs similar to Wistar. However, only captopril normalized LMA increased tone compared with untreated SHRs (15±2% versus 50±3%; P P >0.05). Vasodilatory response of LMAs to Y-27632 was impaired in SHRs compared with Wistar (28±3% versus 81±4%; P P P P P >0.05). These results suggest that ACE inhibition during chronic hypertension reversed vascular dysfunction and hyperconstriction of LMAs that could improve stroke outcome by increasing collateral perfusion.

Background Reproductive events, that is, a preterm birth ( PTB ), small‐for‐gestational‐age infant ( SGA ), and vasomotor symptoms of menopause, are associated with subclinical atherosclerotic cardiovascular disease ( ASCVD ). We evaluated whether women with a past PTB and/or SGA (henceforth PTB / SGA ) were more likely to have severe vasomotor symptoms of menopause and whether the estimated 10‐year ASCVD risk was higher in women with PTB / SGA and vasomotor exposures. Methods and Results We assigned 1866 women (mean age=55±1 years) in the CARDIA (Coronary Artery Risk Development in Young Adults) study to the following categories of reproductive exposures: none, PTB / SGA only, vasomotor symptoms only, or both PTB / SGA and vasomotor symptoms. We used Kruskal‐Wallis tests to evaluate the differences in pooled cohort equation ASCVD risk scores by category and linear regression to evaluate the associations of categories with ASCVD risk scores adjusted for study center, body mass index , education, current hormone replacement therapy use, parity, and hysterectomy. Women with PTB / SGA were more likely to have severe vasomotor symptoms, 36% versus 30%, P ASCVD risk score was higher in women with both PTB / SGA and vasomotor symptoms (4.6%; 95% CI, 4.1%–5.1%) versus women with no exposures (3.3%; 95% CI , 2.9%–3.7%) or vasomotor symptoms only (3.8%; 95% CI , 3.5%–4.0%). ASCVD risk score was higher in women PTB / SGA (4.8%; 95% CI , 3.6%–5.9%) versus no exposures. PTB / SGA and vasomotor symptoms was associated with ASCVD risk score in white women versus no exposures (β=0.40; 95% CI, 0.02–0.78). Conclusions Women with prior PTB / SGA were more likely to have severe vasomotor symptoms of menopause. Reproductive exposures were associated with an estimated 10‐year ASCVD risk in white women.

This study examined cutaneous vasoconstriction to whole-body hypothermia, specifically contributions of neural and endothelial vasomotor responses in glabrous and non-glabrous skin. Eleven participants were semi-recumbent at an ambient temperature of 22 °C for 30 min, after which ambient temperature was decreased to 0 °C until rectal temperature (Tre) had decreased by 0.5 °C. Laser-Doppler fluxmetry was measured at the forehead and thigh for measures of glabrous and non-glabrous skin, respectively; wavelet analysis was performed on the laser-Doppler signal to determine endothelial and neural activities. Hypothermia took on average 97 ± 7 min and caused marked decreases at glabrous (42 ± 5%baseline, p

Context Women are at increased risk for depressive symptoms during the menopause transition. Changes in estradiol secretion and presence of vasomotor symptoms (VMS) contribute to perimenopausal depressive symptoms, but links with progesterone have not been investigated. Objective To determine whether estradiol variability, ovulatory levels of progesterone, and VMS burden are independently associated with perimenopausal depressive symptomatology. Design and Intervention Depressive symptoms, serum levels of estradiol and progesterone, and VMS frequency were assessed weekly in an 8-week observational study. Association of mood with estradiol variability, ovulatory levels of progesterone, and VMS frequency were estimated using generalized estimating equation models. Setting Academic medical center. Patients Fifty unmedicated perimenopausal women with mild-to-moderate depressive symptoms (mean Montgomery-Åsberg Depression Rating Scale [MADRS] score 15.5 ± 5.3). Main Outcome Measure Depressive symptoms (MADRS score). Results During the study, 90.0% of participants had varying estradiol levels, 51.1% had ovulatory progesterone levels, and 90% had VMS. Greater estradiol variability and absence of progesterone levels consistent with ovulation, but not VMS frequency, are associated with higher levels of depressive symptoms (β = 0.11 [95% confidence interval (95% CI), 0.04 to 0.18; P = 0.001]; β = −2.62 [95% CI, −4.52 to −0.71; P = 0.007], respectively), after accounting for higher body mass index, lifetime history of depression, and stressful life events. Conclusions Increasing dysregulation of ovarian hormones, but not VMS, associates with more depressive symptom burden during perimenopause. These results suggest that perimenopausal mood instability is driven by the underlying hormonal dysregulation of the menopause transition involving changes in both estradiol and progesterone.

Purpose: Cognitive decline is commonly reported during the menopausal transition, with memory and attention being particularly affected. The aim of this study was to investigate the effects of a commercially available soy drink on cognitive function and menopausal symptoms in post-menopausal women. Methods: 101 post-menopausal women, aged 44–63 years, were randomly assigned to consume a volume of soy drink providing a low (10 mg/day; control group), medium (35 mg/day), or high (60 mg/day) dose of isoflavones for 12 weeks. Cognitive function (spatial working memory, spatial span, pattern recognition memory, 5-choice reaction time, and match to sample visual search) was assessed using CANTAB pre- and post-the 12 week intervention. Menopausal symptoms were assessed using Greene’s Climacteric Scale. Results: No significant differences were observed between the groups for any of the cognitive function outcomes measured. Soy drink consumption had no effect on menopausal symptoms overall; however, when women were stratified according to the severity of vasomotor symptoms (VMS) at baseline, women with more severe symptoms at baseline in the medium group had a significant reduction (P = 0.001) in VMS post-intervention (mean change from baseline score: − 2.15 ± 1.73) in comparison to those with less severe VMS (mean change from baseline score: 0.06 ± 1.21). Conclusions: Soy drink consumption had no effect on cognitive function in post-menopausal women. Consumption of ~ 350 ml/day (35 mg IFs) for 12 weeks significantly reduced VMS in those with more severe symptoms at baseline. This finding is clinically relevant as soy drinks may provide an alternative, natural, treatment for alleviating VMS, highly prevalent among western women.

Objective We aimed to investigate the effect of omega-3 supplements on relief of vasomotor symptoms among menopausal women. Study design The Cochrane Library, MEDLINE, SCOPUS, EMBASE, ProQuest, Google Scholar, Web of Science, CINAHL, IranMedex and SID databases were searched until September 2017. Inclusion criteria were (1) women were experiencing vasomotor symptoms in the menopause period, (2) intervention was omega-3 supplements (3) randomized controlled trial (RCT) or quasi-RCT, and (4) outcome measures included changes in the frequency and severity of hot flush or night sweats, sleep problems and side effects. Results Three randomized controlled trials involving 483 women in the age range of 51 to 54.7 years were included in the review. Overall, the risk of bias in the included studies was moderate. All the participants were found to be blinded. Meta-analysis of the data showed no difference in the frequency and severity of hot flushes, insomnia severity, sleep quality, quality of life and adverse effects between the two groups. Compared to placebo group, women who received omega-3 supplements experienced lower frequency (mean difference: -1.82, 95% CI: -2.81, -0.83) and severity (mean difference: -.89, 95% CI: -1.25, -0.53) of night sweats. Conclusions RCTs which investigate the impact of omega-3 supplements on vasomotor symptoms in menopausal women are scarce. A comprehensive search in a wide range of databases found only three relevant papers. Our analysis suggests that omega-3 supplements may alleviate night sweats but have no benefit in reducing hot flushes, or improving sleep quality and quality of life during the menopausal period. We recommend high quality RCTs along with a longer follow-up period to investigate this important subject, as there was insufficient evidence to conclude that omega-3 supplements are of benefit in alleviating vasomotor symptoms in menopausal women.

Objective This study was performed to compare the vasomotor symptoms and bone mineral density of postmenopausal women with and without metabolic syndrome. Methods We performed a cross-sectional study of 200 postmenopausal women attending routine health check-ups at Marmara Faculty of Medicine Pendik Training and Research Hospital from June 2015 to December 2015. The vasomotor symptoms scored were hot flashes and night sweats. Metabolic syndrome was defined using the consensus criteria of the International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute. Results Women with vasomotor symptoms had no metabolic syndrome and were younger than those without vasomotor symptoms. There was no significant difference in vasomotor symptoms between patients with osteopenia in the femoral neck, total femur, and spine and patients with normal bone mineral density. The vasomotor symptoms were similar between smokers and nonsmokers. Conclusion The presence of metabolic symptoms is inversely associated with metabolic syndrome in postmenopausal women. Lipid abnormalities and a high body mass index may be important metabolic components associated with these symptoms. No relationship is present between vasomotor symptoms and the bone mineral density of the spine, femoral neck, and total femur.

OBJECTIVE To evaluate efficacy, endometrial safety, and overall safety of a single-capsule 17β-estradiol-progesterone (TX-001HR) for treating menopausal moderate-to-severe vasomotor symptoms. METHODS REPLENISH was a phase 3, 12-month, randomized, double-blind, placebo-controlled, multicenter trial. Women (aged 40-65 years) with vasomotor symptoms and a uterus were randomized to daily estradiol (mg)-progesterone (mg) (1/100, 0.5/100, 0.5/50, or 0.25/50), and women in the vasomotor symptoms substudy (women with moderate-to-severe hot flushes [seven or greater per day or 50 or greater per week]) to those estradiol-progesterone doses or placebo. The primary safety endpoint was endometrial hyperplasia incidence at 12 months in all women (the total population), and the primary efficacy endpoints were frequency and severity changes (from daily diaries) in moderate-to-severe vasomotor symptoms with estradiol-progesterone compared with placebo at weeks 4 and 12 in the vasomotor symptoms substudy. A sample size of 250 women in each active treatment arm with two or less endometrial hyperplasia cases would result in 1% or less annual incidence (upper bound 2.5% or less, one-sided 95% CI). RESULTS One thousand eight hundred forty-five women were enrolled and randomized from August 2013 to October 2015; 1,835 received medication (safety population); 1,255 were eligible for the endometrial safety population; 726 comprised the vasomotor symptoms substudy; their mean age and body mass index were 55 years and 27, respectively; one third were African American. No endometrial hyperplasia was found. Frequency and severity of vasomotor symptoms significantly decreased from baseline with 1 mg estradiol and 100 mg progesterone and 0.5 mg estradiol and 100 mg progesterone compared with placebo at week 4 (frequency: by 40.6 and 35.1 points [1 mg and 100 mg and 0.5 mg and 100 mg, respectively] vs 26.4 points [placebo]; severity: by 0.48 and 0.51 vs 0.34 points) and week 12 (by 55.1 and 53.7 vs 40.2; severity: by 1.12 and 0.90 vs 0.56); 0.5 mg estradiol and 50 mg progesterone improved (P

Author(s): Harrington, LB; Blondon, M; Cushman, M; Kaunitz, AM; Allison, MA; Wang, L; Sullivan, S; Woods, NF; LaCroix, AZ; Heckbert, SR; McKnight, B; Rossouw, J; Smith, NL | Abstract: Essentials Vasomotor symptoms have been proposed as markers of changing cardiovascular risk. In this cohort study, we evaluated these symptoms as markers of venous thrombosis (VT) risk. We found no evidence that vasomotor symptom presence or severity were associated with VT risk. Among these postmenopausal women, vasomotor symptoms are not a useful marker of VT risk. SUMMARY:Background Vasomotor symptoms may be markers of changes in cardiovascular risk, but it is unknown whether these symptoms are associated with the risk of venous thrombosis (VT). Objective To evaluate the association of vasomotor symptom presence and severity with incident VT risk among postmenopausal women, independent of potential explanatory variables. Methods This cohort study included participants of the Women's Health Initiative (WHI) Hormone Therapy Trials (n = 24 508) and Observational Study (n = 87 783), analyzed separately. At baseline, women reported whether hot flashes or night sweats were present and, if so, their severity. Using Cox proportional hazards models, we estimated the VT risk associated with vasomotor symptom presence and severity, adjusted for potential explanatory variables: age, body mass index, smoking status, race/ethnicity, and time-varying current hormone therapy use. Results At baseline, WHI Hormone Therapy Trial participants were aged 64 years and WHI Observational Study participants were aged 63 years, on average. In the WHI Hormone Therapy Trials over a median of 8.2 years of follow-up, 522 women experienced a VT event. In the WHI Observational Study, over 7.9 years of follow-up, 1103 women experienced a VT event. In adjusted analyses, we found no evidence of an association between vasomotor symptom presence (hazard ratio [HR]adj 0.91, 95% confidence interval [CI] 0.75-1.1 in the WHI Hormone Therapy Trials; HRadj 1.1, 95% CI 0.99-1.3 in the WHI Observational Study) or severity (HRadj for severe versus mild 0.99, 95% CI 0.53-1.9 in the WHI Hormone Therapy Trials; HRadj 1.3, 95% CI 0.89-2.0) in the WHI Observational Study) and the risk of incident VT. Conclusions Although vasomotor symptoms have been associated with the risk of other cardiovascular events in published studies, our findings do not suggest that vasomotor symptoms constitute a marker of VT risk.

Objective To investigate the relationship between cerebral vasomotor reactivity (VMR) and acute stroke in patients with internal carotid artery stenosis. Methods 54 patients with internal carotid artery stenosis were enrolled. VMR was calculated by transcranial Doppler monitoring of the velocity of blood flow. 3-Dimensional dynamic contrast enhanced magnetic resonance angiography was used to detect stenosis, and diffusion weighted imaging was used to detect infarction. Results VMR value was significantly lower in patients with carotid artery stenosis than in control group (T = 3.112, P = 0.002), and significantly lower in patients with aortic atherosclerotic stroke than in non-infarct group (T = 10.930, P = 0.000). However, VMR value was significantly higher in patients with new-onset small-artery occlusion stroke than in non-infarction group (T = −2.538, P = 0.013). Scatter plots showed that aortic atherosclerotic stroke occurred mainly in patients with severe internal carotid artery stenosis, and VMR value in cerebral artery significantly decreased. Conclusion Decreased VMR value is an important prognostic factor for the occurrence of aortic atherosclerotic stroke, and can be used as a reference for preoperative hemodynamic evaluation in patients with internal carotid artery stenosis.

OBJECTIVE: Vasomotor symptoms, encompassing hot flashes and night sweats, may be associated with diabetes but evidence is limited. We sought to estimate these associations. METHODS: Among 150,007 postmenopausal Women’s Health Initiative participants from 1993–2014, we prospectively examined associations of incident diabetes with VMS characteristics at enrollment: any vasomotor symptoms, severity (mild/ moderate/severe), type (hot flashes/night sweats), timing (early [pre- or perimenopausal]/late [postmenopausal]), and duration. Cox proportional hazards models estimated hazard ratios (HRs) and 95% CIs. RESULTS: Mean duration of follow-up was 13.1 years. VMS prevalence was 33%. Reporting any VMS was associated with 18% increased diabetes risk (95% CI 1.14, 1.22), which increased with severity (mild: HR=1.13, 95% CI 1.08, 1.17; moderate: HR=1.29, 95% CI 1.22, 1.36; severe: HR=1.48, 95% CI 1.34, 1.62) and duration (4% per 5-years, 95% CI 1.03, 1.05), independent of obesity. Diabetes risk was more pronounced for women reporting any night sweats (night sweats only: HR=1.20, 95% CI 1.13, 1.26; night sweats and hot flashes: HR=1.22, 95% CI 1.17, 1.27) than only hot flashes (HR=1.08, 95% CI 1.02, 1.15) and was restricted to late VMS (late: HR=1.12, 95% CI 1.07, 1.18; early and late: HR=1.16, 95% CI 1.11, 1.22; early: HR=0.99, 95% CI 0.95, 1.04). CONCLUSIONS: VMS are associated with elevated diabetes risk, particularly for women reporting night sweats and postmenopausal symptoms. The menopausal transition may be an optimal window for clinicians to discuss long-term cardiovascular/metabolic risk with patients and leverage the bother of existing symptoms for behavior change to improve VMS and reduce diabetes risk.

BACKGROUND Hydrogen sulfide (H2S) has anti-inflammatory and anti-hypertensive effects, and connexins (Cxs) are involved in regulation of immune homeostasis. In this study, we explored whether exogenous H2S prevents hypertensive inflammation by regulating Cxs expression of T lymphocytes in spontaneously hypertensive rats (SHR). MATERIAL AND METHODS We treated SHR with sodium hydrosulfide (NaHS) for 9 weeks. Vehicle-treated Wistar-Kyoto rats (WKYs) were used as a control. The arterial pressure was monitored by the tail-cuff method, and vascular function in basilar arteries was examined by pressure myography. Hematoxylin and eosin staining was used to show vascular remodeling and renal injury. The percentage of T cell subtypes in peripheral blood, surface expressions of Cx40/Cx43 on T cell subtypes, and serum cytokines level were determined by flow cytometry or ELISA. Expression of Cx40/Cx43 proteins in peripheral blood lymphocytes was analyzed by Western blot. RESULTS Chronic NaHS treatment significantly attenuated blood pressure elevation, and inhibited inflammation of target organs, vascular remodeling, and renal injury in SHR. Exogenous NaHS also improved vascular function by attenuating KCl-stimulated vasoconstrictor response in basilar arteries of SHR. In addition, chronic NaHS administration significantly suppressed inflammation of peripheral blood in SHR, as evidenced by the decreased serum levels of IL-2, IL-6, and CD4/CD8 ratio and the increased IL-10 level and percentage of regulatory T cells. NaHS treatment decreased hypertension-induced Cx40/Cx43 expressions in T lymphocytes from SHR. CONCLUSIONS Our data demonstrate that H2S reduces hypertensive inflammation, at least partly due to regulation of T cell subsets balance by Cx40/Cx43 expressions inhibition.

NEW FINDINGS What is the central question of this study? Premenopausal women have an attenuated inspiratory muscle metaboreflex-induced increase in arterial blood pressure compared with men. It is unclear whether sympathetic vasomotor outflow during dynamic exercise with increased inspiratory muscle activation is less in young women than in men. What is the main finding and its importance? The magnitude of increased sympathetic vasomotor outflow during leg cycling with inspiratory resistance was smaller in women than in men. Less sympathetic vasomotor outflow with inspiratory muscle metaboreflex activation could be one of the mechanisms for the attenuated inspiratory muscle-induced metaboreflex during exercise in young women. ABSTRACT We compared changes in muscle sympathetic nerve activity (MSNA) and cardiovascular variables during leg cycle exercise with increased inspiratory muscle resistance in men and women. We hypothesized that sympathetic vasomotor outflow during exercise with increased inspiratory resistance would be attenuated in young women compared with age-matched men. Eight women and seven men completed the study. The subjects performed two 10 min exercise bouts at 40% peak oxygen uptake using a cycle ergometer in a semirecumbent position [spontaneous breathing for 5 min and voluntary hyperventilation with or without inspiratory resistive breathing for 5 min (breathing frequency 50 breaths min-1 with a 50% duty cycle; inspiratory resistance 30% of maximal inspiratory pressure)]. Mean arterial blood pressure (MAP) was acquired using finger photoplethysmography. The MSNA was recorded via microneurography of the right median nerve at the cubital fossa. During leg cycle exercise with inspiratory resistive breathing, MSNA burst frequency was increased, accompanied by an increase in MAP in both men and women. Women, compared with men, had less of an increase in MAP (women +22.8 ± 12.3 mmHg versus men +32.2 ± 5.4 mmHg; P

Vasomotor symptoms (VMS) are a common side effect of breast cancer treatment, yet modifiable factors that may predict VMS among breast cancer survivors are unknown. We estimated multivariable-adjusted odds ratios and 95% confidence intervals (aOR, 95% CI) for predictors of VMS among 3595 breast cancer survivors enrolled in the Life and Longevity after Cancer (LILAC) study, an ancillary study of the Women’s Health Initiative (WHI). VMS post-diagnosis were reported by 790 (22.0%) participants. Risk of VMS after diagnosis was positively associated with prior chemotherapy (aOR 1.80, 95% CI 1.21–2.68) and adjuvant hormone therapy (aOR 2.73, 95% CI 2.08–3.58), postmenopausal hormone therapy use (aOR 1.67, 95% CI 1.30–2.13), prior VMS (aOR 2.20, 95% CI 1.73–2.80), bilateral oophorectomy (aOR 1.77, 95% CI 1.37–2.27), and baseline antidepressant use (aOR 1.49, 1.06–2.09). VMS post-diagnosis were less likely among younger women (aOR 0.94, 95% CI 0.93–0.96), women younger at menopause (aOR 0.98, 95% CI 0.97–1.00), women with more time since diagnosis (aOR 0.92, 95% CI 0.90–0.94), and diabetics (aOR 0.45, 95% CI 0.21–0.95). Metabolic syndrome was not associated with post-diagnosis VMS (aOR 0.76, 95% CI 0.45–1.28). VMS following breast cancer diagnosis was related to a number of modifiable factors, but was unrelated to metabolic syndrome. Identification of factors that predispose women to VMS following a breast cancer diagnosis may allow clinicians to recognize and address VMS in the subset of women who are most likely to experience such symptoms.

Background Middle-aged women experience various menopausal symptoms during the menopause. These symptoms can affect their quality of life and health. Several epidemiological studies reported that obesity associates with menopausal symptoms. The aim of this cross-sectional study was to examine the associations between obesity and multiple menopausal symptoms at different stages of menopause in middle-aged Korean women. Methods The study population included women aged 44–56 years who visited a tertiary referral hospital for medical check-ups between November 2012 and March 2013 and were free from serious illness, could comprehend a questionnaire. The Menopause-Specific Quality of Life (MENQOL) questionnaire was used to assess the prevalence of menopausal symptoms. Overweight and obesity were defined as body mass index (BMI) of 23–24.9 and ≥25 kg/m2, respectively. Results Of the 2204 middle-aged women, 929 met the eligibility criteria. Of these, 533 (57.4%) and 396 (42.6%) were in perimenopause and postmenopause, respectively. In perimenopause, obese women were significantly more likely to have moderate/severe physical symptoms (MENQOL domain score ≥ 5) than normal or overweight women. In postmenopause, obese women were significantly more likely to have moderate/severe vasomotor symptoms. Multiple linear regression with adjustment for confounders showed that relative to normal weight, obesity in perimenopause and postmenopause associated independently with physical symptoms (beta coefficient = 0.35; P = 0.023) and vasomotor symptoms (beta coefficient = 0.68; P = 0.003), respectively. Overweight did not associate with menopausal symptoms. BMI did not associate significantly with psychosocial or sexual symptoms at either stage of menopause. Conclusions Obese women had more frequent menopausal symptoms than normal or overweight women but the associated menopausal symptom differed depending on the menopausal stage. Further studies are required to confirm this result and identify the underlying mechanisms. Electronic supplementary material The online version of this article (doi:10.1186/s12905-017-0487-7) contains supplementary material, which is available to authorized users.