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Background The influence of repeated exposures to cold pain stimulus, a surrogate of clinical pain, has remained largely unexplored. The study was planned to test the effect of repeated exposures to cold pain through cold pressor task on pain sensitivity and vascular reactivity. Methods Single-group experimental study. Thirty-seven healthy male volunteers (18–25 years) were exposed to cold pressor tasks for seven consecutive days and on the 14th day on the nondominant hand. The same was repeated on dominant hand on first and seventh days; 31 completed the protocol. Results Pain threshold and tolerance in the nondominant hand increased from day 1 to day 7 (p ρ =0.45, p = 0.011) and day 7 ( ρ =0.38, p = 0.036). Diastolic blood pressure response was found to increase by day 7 (p Conclusion Habituation in pain threshold and tolerance was observed on repeated exposure to cold pain, which was not significantly retained till the 14th day. The same was not observed with subjective feeling of pain perception. The increased diastolic blood pressure response is suggestive of peripheral vasoconstriction. Increased tolerance in the dominant hand by day 7 demonstrates a systemic effect in habituation.

Traumatic brain injury (TBI) represents a critical public health problem around the world. To date, there are no accurate therapeutic approaches for the management of cardiovascular impairments induce by TBI. In this regard, hydrogen sulfide (H

Breath-by-breath oxygen-carbon dioxide (O2-CO2) exchange ratio (bER) is a respiratory gas exchange (RGE) metric, which is the ratio of the changes in the partial pressure of O2 (ΔPO2) to CO2 (ΔPCO2...

Introdution: Endothelium integrity is a key that maintains vascular homeostasis but it can suffer irreversible damage by blood pressure changes, reflecting an imbalance in the maintenance of vascul...

Physical inactivity in youth is one of the major concerns in today’s world because the technological developments in various areas have made them lethargic, since just clicking a button fulfills most of their daily requirements. Sedentary behavior that is prolonged sitting with no physical activity is the reason behind numerous physiological diseases in human beings such as obesity, diabetes, cardio-vascular disorders, anxiety, colon cancer etc. around the world. Therefore, for a healthy living, it is suggested to do a minimum amount of health enhancing physical activity daily. In this research, we generated a dataset with information regarding sedentary behavior and physical activity and its impact on the overall health of the young subjects. International physical activity questionnaire and a basic body examination based on the metabolic equivalent’s min/week scores are used to collect this information. Several machine-learning techniques namely k-nearest neighbor, linear discriminant analysis, decision tree, support vector machine and Random forest are implemented for identifying and classifying the subjects in terms of sedentary and physically active groups. Healthiness in terms of cardio-vascular activities of the subjects based on their sedentary and physically active behaviors are determined in this paper, the evaluation criteria used for monitoring heart health is heart rate variability.

espanolEl verbascosido, tambien denominado acteosido, se ha encontrado en mas de 23 familias de plantas, demostrando, entre muchas otras propiedades, utilidad in vivo como antihipertensivo. Sin embargo, su efecto en el sistema vascular no es conocido por completo. Este trabajo tiene como objetivo el estudio de la reactividad vascular del verbascosido sobre aorta de rata, hipotetizando un posible efecto relajante vascular responsable de la actividad antihipertensiva. Las curvas concentracion-respuesta se llevaron a cabo sobre anillos de 3mm de longitud de aorta de rata, evaluando la respuesta a verbascosido y a fenilefrina, acetilcolina, nitroprusiato sodico y calcio en presencia de verbascosido a diferentes concentraciones molares (10-6, 10-5 y 10-4 M). Los resultados obtenidos muestran que el verbascosido, in vitro, no tiene un efecto relajante vascular y no afecta al tono basal de la aorta, no potencia la accion contracturante de la fenilefrina, pero, no obstante, si reduce la relajacion vascular derivada de acetilcolina. Por otro lado, potencia ligeramente la accion relajante vascular del nitroprusiato, no interfiriendo en la entrada de calcio extracelular. Asi pues, la actividad antihipertensiva in vivo del verbascosido no se explica a traves de la actividad in vitro vista en estos experimentos. EnglishVerbascoside, also known as Acteoside, has been found in over 23 families of plants. demonstrating, among many other properties, utility in vivo as an antihypertensive. However, its effect on the vascular system is not fully known. This work aims to study the vascular reactivity of verbascoside on rat aorta, hypothesizing a possible vascular relaxing effect responsible for the antihypertensive activity. The concentration-response curves were carried out on 3mm long rings of rat aorta, evaluating the response to verbascoside and phenylephrine, acetylcholine, sodium nitroprusside and calcium in the presence of verbascoside at different molar concentrations (10-6, 10-5 y 10-4 M). The results obtained show that verbascoside, in vitro, does not have a vascular relaxing effect and does not affect the basal tone of the aorta, it does not enhance the contracting action of phenylephrine, but nevertheless it does reduce the vascular relaxation derived from acetylcholine. On the other hand, it slightly enhances the vascular relaxing action of nitroprusside, not interfering with the entry of extracellular calcium. Thus, the antihypertensive in vivo activity of verbascoside is not explained by the in vitro activity seen in these experiments.

The review presents the rationale for the importance of studies on the reactivity of cerebral vessels, the classification of cerebrovascular reactivity (CVR) and the threshold values of quantitative indicators of the reserve phase and autoregulation of cerebral blood flow in healthy volunteers. Features of CVR in hypertension are described depending on the clinical course, daily blood pressure profile, the presence of comorbid pathology, the treatment approaches in treatment CVR disorders. We discuss the evidence-based data on the role of CVR assessment in diagnosing latent cerebral circulation insufficiency, prediction of cerebrovascular complications, monitoring the effectiveness and safety of drug and devise-based therapy of hypertension associated with abnormal CVR.

Digital thermal monitoring (DTM) is an alternative, noninvasive, methodology to evaluate endothelial function using temperature change on finger as a surrogate measure of the magnitude of vascular reactivity index (VRI). A most recent modification to the technique includes the application of occlusion cuff at the base of a finger. We evaluated the validity of DTM compared with the standard flow‐mediated dilation (FMD) protocol. Thirty‐eight (22 males; 38 ± 15 years) participants were studied. Occlusion cuff was placed over the right antecubital fossa or at the base of the right index finger. Temperature monitors were placed on bilateral index fingers to assess change in temperature throughout 5‐min occlusion and recovery phases. VRI values obtained with the finger occlusion (1.58 ± 0.29 AU) were not significantly different from VRI measured with the brachial artery occlusion (1.55 ± 0.26 AU; p = .47), and the agreement of VRI values was confirmed in the Bland‐Altman plot with a mean difference of −0.03 ± 0.34 (95% confidence interval: −0.15 to 0.09). Shear rateAUCI was significantly correlated with VRI obtained from brachial occlusion (r = .34) and finger occlusion VRI (r = .54; all p

Objetivo: analisar os efeitos da prática da caminhada em hipertensos. Métodos: revisão integrativa da literatura em língua portuguesa, efetuada nas bases de dados SciELO e Lilacs – BVS. Realizou-se uma revisão em sete artigos publicados entre os anos de 2010 e 2020. Resultados: o estudo revelou que a prática da caminhada é efetiva para redução dos níveis pressóricos em diferentes contextos e intensidades no controle da hipertensão, seja com efeitos agudos e/ou crônicos, sendo assim considerada uma ferramenta não medicamentosa, pois condiciona o sistema cardiovascular a responder fisiologicamente com diminuição da reatividade vascular, mesmo em situações de estresse, induzindo a diminuição na pressão arterial. Conclusão: a pesquisa apontou que a caminhada tem efeitos positivos sobre os níveis pressóricos, uma vez que a mesma contribuiu significativamente para o controle da hipertensão arterial sistêmica, especialmente naquelas que tiveram acompanhamento de um profissional de educação física. Sugere-se a proposição de novas pesquisas que levem em consideração não só a atuação desse profissional, mas também utilize outras variáveis, como diferentes modalidades de atividade física, dieta alimentar, níveis de estresse e qualidade do sono.

Background: Hypercholesterolemia is one of the most important risk factors for atherosclerosis and subsequent cardiovascular disease (CVD). CVD is the leading cause of cardiovascular morbidity and mortality worldwide, currently, there is a major trend to use herbal remedies for the treatment and prevention of hypercholesterolemia. Objective: In the present work, we investigated the effect of aqueous green tea extract on lipid profile and vascular reactivity & changes in body weight in hypercholesterolemic albino rats Materials and methods: Adult male albino rats were chosen as an animal model for this study. Rats were brought from animal house, Faculty of Medicine, Assiut University, Assiut, Egypt, and were maintained on a balanced diet with water supply freely in clean containers. They were kept for two weeks to adapt to the laboratory conditions before the start of the experiment. Forty age-matched male albino rats with initial body weights ranging from 200 to 220g were used. Results: In group (III & IV), total cholesterol, LDL, and triglyceride levels were significantly decreased respectively& HDL were significantly increased compared with the group II (p < 0.05). also in group (III & IV) the aortic contractility is decreased and aortic relaxation were significantly increased compared with the group II (p < 0.05) & body weight was decreased significantly (p < 0.05) in group IV compared with the group II. Conclusion: The results obtained by the present study showed that administration of aqueous green tea extract to the hypercholsterolemic rats has a role in improvement of plasma lipids, vascular reactivity& body weight.

Introduction . Preoperative fMRI often shows a reduced BOLD response in the areas located perifocal to brain tumors caused by pathological vasoreactivity as a result of neurovascular uncoupling. The aim of this study was an accurate identification of the eloquent cortical areas near brain tumors by measuring vasoreactivity using the breath holding test. Material and methods. 23 patients with brain tumors located near eloquent cortical areas underwent fMRI mapping of the language and / or motor cortical areas depending on the location of the tumor. Breath hold test was also included, the design of which coincided with motor and language block paradigms. Results . A statistical dependency between motor, speech tasks and breath-hold BOLD-response was included into the BOLD analysis using coherence. fMRI activation maps generated by this method showed activation in the eloquent areas adjacent to brain tumors which were not detected by the standard analysis. This study shows that neurovascular uncoupling affects the accuracy of BOLD fMRI in brain tumors. Conclusion. The results of fMRI mapping can be partially improved by the incorporating vasoreactivity measurements into a standard analysis.

The use of repeatedly heated frying oil is hazardous to health, due to oxidative process that occurs in the oil. Addition of an additive with antioxidant property could lessen the detrimental effects of repeated frying in the oils. Citrus leaf extract (CLE) supplementation was reported to possess antioxidant and blood pressure-lowering properties. Our study aimed to determine the effects of CLE addition into frying oil in rats fed with repeatedly heated oil diet. Seven groups of male Sprague-Dawley rats were given fresh and heated oil diets (five-time- and ten-time-heated palm oil), with and without the CLE addition for 16 weeks. CLE addition decreased peroxide value and augmented the total phenolics content in the heated oils. CLE addition reversed the negative effects of heated oil on nitric oxide level, systolic blood pressure, and vascular reactivity. In conclusion, these findings show that CLE has the ability to reduce oxidative damage caused by thermal degradation in frying oil and subsequently lowers the risk of hypertension in rats that consumed heated oil.

Oxidative stress is the main player in the development of diabetic vascular complications. Co-Q10 is a natural antioxidant present in the body and in many foods. This study was designed to evaluate the effect of Co-Q10 administration to improve vascular complications and increase insulin sensitivity in diabetic rats. Fifty male rats were divided into five groups: control, diabetic untreated, diabetic insulin-treated, diabetic Co-Q10-treated, and diabetic combined-treated groups. After 8 weeks, blood pressure and vascular reactivity to NE and ACh, fasting glucose, insulin, C-peptide, MDA, TAC, HbA1c, and the HOMA-IR were measured. Diabetes increased fasting glucose, HbA1c, HOMA-IR, MDA, blood pressure, and decreased TAC and vascular reactivity. Ttreatment with insulin or Co-Q10 improved glycemic parameters and increasing antioxidant levels compared to diabetic group. Combined Co-Q10 with insulin was found to increase insulin sensitivity and decrease its resistance, which helps to decrease insulin doses in diabetic patients and reduce its side effects.

OBJECTIVE To investigate the effects of aerobic exercise on the cardiac baroreflex function and vascular reactivity in patients with cirrhosis. METHODS Thirteen patients with cirrhosis were submitted to exercise and control intervention. At baseline and at 30 and 60 min following intervention, we evaluated cardiac baroreflex sensitivity (cBRS) and the baroreflex effectiveness index (BEI) using sequence technique. Vascular reactivity was assessed inducing reactive hyperemia before and 60 min after intervention. RESULTS At baseline, there was no difference (P interaction = 0.848) between exercise (from 3.0 ± 0.34 to 14.60 ± 1.06 ml/100ml/min) and control sessions (from 2.38 ± 0.10 to 13.73 ± 1.05 ml/100ml/min) regarding the increase in forearm blood flow during reactive hyperemia. However, this response was higher postexercise (from 3.38 ± 0.31 to 16.58 ± 1.58 ml/100ml/min) than postcontrol intervention (from 2.04 ± 0.23 to 11.98 ± 1.16 ml/100ml/min, P interaction

Nelson Ivan Cupitra, Juan C Calderón, Raul Narvaez-Sanchez Physiology and Biochemistry Research Group-PHYSIS, Faculty of Medicine, University of Antioquia, Medellin, ColombiaCorrespondence: Raul Narvaez-Sanchez Carrera 51 D #62-29, Office 203, Medellin, ColombiaTel +57 42196030Email raul.narvaez@udea.edu.coAim: To contribute to the knowledge about the mechanisms involved in aortic stiffness due to ageing.Materials and Methods: Aortic rings from young (1.5± 0.5 months, 0.8± 0.2 kg), adult (6± 0.5 months, 2.7± 0.5 kg) and old (28± 8 months, 3.2± 0.8 kg) male New Zealandrabbits were used to evaluate: 1) intima-media thickness by optical microscopy; 2) vascular reactivity (VR) in terms of sensitivity (pD2) and efficacy (Emax) to KCl; phenylephrine (PE); U-46619, a thromboxane A2 receptor agonist, TXA2; carbachol (CCh), isoproterenol and sodium nitroprusside (SNP), using organ bath experiments; and 3) the expression of receptors α 1, β 2 and thromboxane-prostanoids (TP), by immunofluorescence.Results: Ageing 1) did not change the thickness of tunica; 2) significantly reduced the pD2 to KCl, increased the pD2 to PE and reduced both the pD2 and Emax to TXA2, CCh and isoproterenol, and reduced the pD2 to SNP; and 3) significantly increased the expression of α 1 and β 2 receptors in the intima and adventitia, and the expression of TP only in the adventitia.Conclusion: Our results suggest that ageing makes the aorta more reactive to α 1 adrenergic contraction, and it could be a compensation for lower responsiveness to prostanoids. The aged aorta is less reactive to endothelium-dependent and non-dependent relaxation, and the vessel seems to try to compensate for that stiffness increasing β 2 receptors, although probably less functional. These results complement the proposed mechanisms of elastocalcinosis and smooth muscle rigidity, expanding the vision that should guide the treatment of aortic stiffness due to aging.Keywords: ageing, aortic rings, vascular reactivity, vascular smooth muscle, vascular stiffness

Background: Vasoplegia is vascular hyporesponsiveness to vasopressors and is an important phenomenon in children with refractory septic shock. This study aimed to develop an objective formula correlated with vasoplegia and evaluate the predictive power for mortality in children with refractory septic shock. Materials and Methods: We retrospectively analyzed children with refractory septic shock admitted to a pediatric intensive care unit (PICU) and monitored their hemodynamics via a pulse index continuous cardiac output (PiCCO) system. Serial hemodynamic data including cardiac index (CI), systemic vascular resistant index (SVRI) and vasoactive-inotropic score (VIS) were recorded during the first 72 hours after PICU admission. We defined vascular reactivity index (VRI) as SVRI/VIS and analyzed the effect of VRI in predicting mortality in children with refractory septic shock. Results: Thirty-three children with refractory septic shock were enrolled. The SVRI was lower in the mortality group compared to the survival group ( P < .05). The average area under the receiver operating characteristic curve of VRI within the first 72 hours was 0.8 and the serial values of VRI were significantly lower in the mortality group during the period from 0 to 48 hours ( P < .05). However, there were no significant differences in serial CI values between the survival and mortality groups. Conclusions: Vasoactive-inotropic score may potentially be used to quantify the severity of vasoplegia based on the clinical response of vessels after resuscitation with vasopressors. Lower VRI levels may indicate a higher risk of mortality in children with septic shock.

In this study, task-related stress induction through Stroop task and social stress induction protocol based on elements of Trier Social Stress Test are examined. The aim of the paper is to find the optimal combination of social and task-related stress to be used to consistently and reliably induce a stressful reaction. In total 16 healthy subjects participated in this study that seeks to find and compare the different stressors and their relation to physiological reactivity. Our findings show that electrodermal activity measurements are suitable when using a combination of stressors while heart rate and Root Mean Square of the Successive Differences highlight a greater reactivity to task-stress.

Case Description An 82-year-old man with dementia, gait disturbance, and a small cerebral infarction owing to severe bilateral carotid artery stenosis was successfully treated with carotid artery stenting (CAS). Preoperative cerebral vascular reactivity was reduced in the bilateral cerebral hemispheres. We performed CAS to treat right internal carotid artery stenosis. Following CAS, cerebral vascular reactivity showed an increase in the bilateral cerebral hemispheres. Memory, fluency, and attention also showed improvement. Conclusions This case illustrates the potential benefit of single-stage CAS for cognitive function in severe bilateral carotid artery stenosis without hyperperfusion syndrome.

Adiponectin has an important role in obesity, insulin resistance, and cardiovascular disease. We investigated the association between serum adiponectin levels and endothelial function in kidney transplant patients.Fasting blood samples were obtained from 70 kidney transplant patients. The vascular reactivity index was measured with a digital thermal monitoring test. Serum adiponectin levels were measured with a commercially available enzyme immunoassay kit. A vascular reactivity index1.0 was defined as poor, 1.0 or greater but less than 2.0 was intermediate, and 2.0 or greater was good.The results showed that 10 kidney transplant patients (13.3%) were categorized with a vascular reactivity index of poor, 25 (35.7%) were intermediate, and 35 (50%) were good. Increased waist circumference (P = .037), increased serum alkaline phosphatase (P = .026), and lower serum adiponectin (P = .001) were associated with poor vascular reactivity index. Advanced age (r = -0.300; P = .012), waist circumference (r = -0.372; P = .002), serum alkaline phosphatase (r = -0.323; P = .006), and logarithmically transformed serum triglycerides (r = -0.317; P = .007) were negatively correlated with the vascular reactivity index, whereas serum adiponectin (r = 0.332; P = .005) was positively correlated with the vascular reactivity index. Multi variable forward stepwise linear regression analysis showed that waist circumference, serum alkaline phosphatase, and serum adiponectin were significantly and independently associated with the vascular reactivity index.Fasting serum adiponectin levels were positively associated with the vascular reactivity index and negatively associated with endothelial function in kidney transplant patients.

BackgroundObstructive sleep apnoea and the related intermittent hypoxia (IH) are widely recognised as risk factors for incident cardiovascular diseases. Numerous studies support the deleterious vascular impact of IH in rodents but an overall interpretation is challenging owing to heterogeneity in rodent species investigated and the severity and duration of IH exposure. To clarify this major issue, we conducted a systematic review and meta-analysis to quantify the impact of IH on systemic artery structure and function depending on the different IH exposure designs.MethodsWe searched PubMed, Embase and Web of Science, and included 125 articles in a meta-analysis, among them 112 using wild-type rodents and 13 using apolipoprotein E knockout (ApoE−/−) mice. We used the standardised mean difference (SMD) to compare results between studies.ResultsIH significantly increased mean arterial pressure (+13.90 (95% CI 11.88–15.92) mmHg), and systolic and diastolic blood pressure. Meta-regressions showed that mean arterial pressure change was associated with strain and year of publication. IH altered vasodilation in males but not in females and increased endothelin-1-induced but not phenylephrine-induced vasoconstriction. Intima–media thickness significantly increased upon IH exposure (SMD 1.10 (95% CI 0.58–1.62); absolute values +5.23 (2.81–7.84) µm). This increase was observed in mice but not in rats and was negatively associated with age. Finally, IH increased atherosclerotic plaque size in ApoE−/− mice (SMD 1.08 (95% CI 0.80–1.37)).ConclusionsOur meta-analysis established that IH, independently of other confounders, has a strong effect on vascular structure and physiology. Our findings support the interest of identifying and treating sleep apnoea in routine cardiology practice.

This study shows ChAT-expressing T cells can induce vasodilation of the blood vessel in the coronary circulation and that this effect relies on a direct interaction between T cells and the coronary vascular endothelium. The study establishes a potential immunomodulatory role for T cells in the coronary circulation. The present findings offer an additional possibility that a deficiency of ChAT-expressing T cells could contribute to reduced coronary blood flow and ischemic events in the myocardium.

Objective: The aim of this study was to clarify the role of autophagy in stellate ganglion block (SGB) reversing posthemorrhagic shock mesenteric lymph (PHSML)-mediated vascular hyporeactivity.Methods: Hemorrhagic shock model in conscious rats was employed to observe the effects of SGB (0.2 ml of 0.25% ropivacaine hydrochloride hydrate) and autophagy inhibitor 3-methyladenine (3-MA; 30 mg/kg) on the vascular reactivity of second-order rat mesenteric arteries in vitro, while the effects of PHSML (1 ml/kg) and autophagy agonist rapamycin (Rapa, 10 mg/kg) on the beneficial effect of SGB were investigated. The cellular viability, contractility, and autophagy-related protein expressions in vascular smooth muscle cells (VSMCs) were detected following treatments of PHSML, PHSML obtained from the rats that underwent hemorrhagic shock plus SGB (PHSML-SGB), and PHSML plus 3-MA (5 mM), respectively.Results: Hemorrhagic shock significantly decreased the vascular reactivity to gradient norepinephrine (NE), which is reversed by the SGB treatment and 3-MA administration. On the contrary, PHSML intravenous infusion and Rapa administration inhibited the vascular contractile responses in rats that underwent hemorrhagic shock plus SGB treatment. PHSML treatment significantly inhibited the cellular viability and contractility in VSMCs, increased the expressions of LC3-II and Beclin 1, and decreased the expression of p62, along with opposite appearances in these indices following PHSML-SGB treatment. In addition, 3-MA counteracted the adverse roles of PHSML in these indices in VSMCs.Conclusion: SGB inhibits PHSML-mediated vascular hyporeactivity by reducing the excessive autophagy in VSMCs.

This study aimed to investigate the effects of the combined injectable contraceptive (CIC) containing estradiol valerate (EV) and norethisterone enanthate (NET-EN) on aorta function and morphology, as well as on redox status, of female Wistar rats. Female rats (9-10 weeks of age) received intramuscular injections of CIC (0.1 mg EV plus 1 mg NET-EN) or castor oil (control group, CTL) for 8 weeks, once a week. Food intake, body weight and systolic blood pressure were measured during the treatment period. Thoracic aortic segments were prepared for isometric tension recording and morphological analysis. Redox status was evaluated by total oxidant status (TOS) and lipid peroxidation (LP) on plasma and reduced glutathione (GSH) on whole blood. CIC group presented lower food intake and lower total weight gain compared to CTL group. There was no change in systolic blood pressure, vascular response of aorta to phenylephrine and acetylcholine and aorta thickness. Plasma TOS and LP values were reduced in CIC group, although GSH was not altered. It was shown that the long-term treatment with the CIC containing EV plus NET-EN does not induce endothelial dysfunction and histomorphometric changes of vascular wall, as well as improves redox status on female Wistar rats.

Intermittent hypoxia (IH) leads to vascular dysfunction, and O‑linked‑β‑N‑acetylglucosamine (O‑GlcNAc)ylation may regulate vascular reactivity through the modulation of intracellular signaling. The present study hypothesized that O‑GlcNAc modifications contributed to the vascular effects of acute IH (AIH) and chronic IH (CIH) through the MAPK and Ca2+/calmodulin‑dependent kinase II (CaMKII) pathways. Rat aortic and mesenteric segments were incubated with DMSO, O‑GlcNAcase (OGA) or O‑GlcNAc transferase (OGT) inhibitor under either normoxic or AIH conditions for 3 h, and arterial function was then assessed. Meanwhile, arteries isolated from control and CIH rats were exposed to 3 h of incubation under normoxic conditions using DMSO, OGA or OGT as an inhibitor, before assessing arterial reactivity. CIH was found to increase the expression of vascular O‑GlcNAc protein and OGT, phosphorylate p38 MAPK and ERK1/2, and decrease OGA levels, but it had no effects on phosphorylated CaMKII levels. OGA inhibition increased global O‑GlcNAcylation and the phosphorylation of p38 MAPK, ERK1/2 and CaMKII, whereas OGT blockade had the opposite effects. OGA inhibition preserved acetylcholine‑induced relaxation in AIH arteries, whereas OGT blockade attenuated the relaxation responses of arteries under normoxic conditions or undergoing AIH treatments. However, the impairment of acetylcholine dilation in CIH mesenteric arteries was improved. CIH artery contraction was increased following angiotensin II (Ang II) exposure. Blockade of p38 MAPK and ERK1/2, but not CaMKII, attenuated Ang II‑induced contractile responses in CIH arteries isolated from the non‑OGT inhibitor‑treated groups. OGT inhibition significantly blocked contractile responses to Ang II and abolished the inhibitory effects of MAPK inhibitors. These findings indicated that O‑GlcNAcylation regulates IH‑induced vascular dysfunction, at least partly by modulating MAPK, but not CaMKII, signaling pathways.

BackgroundThe protective effect of estrogen on the vasculature cannot be explained only by its action through the receptors ERα and ERβ. G protein-coupled estrogen receptors (GPER)—which are widely distributed throughout the cardiovascular system—may also be involved in this response. However, little is known about GPER actions in hypertension. Therefore, in this study we evaluated the vascular response mediated by GPER using a specific agonist, G-1, in spontaneously hypertensive rats (SHR). We hypothesized that G-1 would induce a relaxing response in resistance mesenteric arteries from SHR of both sexes.MethodsG-1 concentration-response curves (1 nM-10 μM) were performed in mesenteric arteries from SHR of both sexes (10–12-weeks-old, weighing 180–250 g). The effects of G-1 were evaluated before and after endothelial removal and incubation for 30 min with the inhibitors L-NAME (300 μM) and indomethacin (10 μM) alone or combined with clotrimazole (0.75 μM) or catalase (1,000 units/mL). GPER immunolocalization was also investigated, and vascular hydrogen peroxide (H2O2) and ROS were evaluated using dichlorofluorescein (DCF) and dihydroethidium (DHE) staining, respectively.ResultsGPER activation promoted a similar relaxing response in resistance mesenteric arteries of female and male hypertensive rats, but with the participation of different endothelial mediators. Males appear to be more dependent on the NO pathway, followed by the H2O2 pathway, and females on the endothelium and H2O2 pathway.ConclusionThese findings show that the GPER agonist G-1 can induce a relaxing response in mesenteric arteries from hypertensive rats of both sexes in a similar way, albeit with differential participation of endothelial mediators. These results contribute to the understanding of GPER activation on resistance mesenteric arteries in essential hypertension.

The carry-over of zearalenone (ZEN) to the myocardium and its effects on coronary vascular reactivity in vivo have not been addressed in the literature to date. Therefore, the objective of this study was to verify the hypothesis that low ZEN doses (MABEL, NOAEL and LOAEL) administered per os to prepubertal gilts for 21 days affect the accumulation of ZEN, α-ZEL and β-ZEL in the myocardium and the reactivity of the porcine coronary arteries to vasoconstrictors: acetylcholine, potassium chloride and vasodilator sodium nitroprusside. The contractile response to acetylcholine in the presence of a cyclooxygenase (COX) inhibitor, indomethacin and / or an endothelial nitric oxide synthase (e-NOS) inhibitor, L-NAME was also studied. The results of this study indicate that the carry-over of ZEN and its metabolites to the myocardium is a highly individualized process that occurs even at very low mycotoxin concentrations. The concentrations of the accumulated ZEN metabolites are inversely proportional to each other due to biotransformation processes. The levels of vasoconstrictors, acetylcholine and potassium chloride, were examined in the left anterior descending branch of the porcine coronary artery after oral administration of ZEN. The LOAEL dose clearly decreased vasoconstriction in response to both potassium chloride and acetylcholine (P &lt, 0.05 for all values) and increased vasodilation in the presence of sodium nitroprusside (P = 0.021). The NOAEL dose significantly increased vasoconstriction caused by acetylcholine (P &lt, 0.04), whereas the MABEL dose did not cause significant changes in the vascular response. Unlike higher doses of ZEN, 5 μg/kg had no negative influence on the vascular system.

BACKGROUND Portal hypertension (PHT) is primarily caused by an increase in resistance to portal outflow and secondarily by an increase in splanchnic blood flow. Vascular hyporeactivity both in systemic circulation and in the mesenteric artery plays a role in the hyperdynamic circulatory syndrome. AIM To explore gender differences and the role of endogenous sex hormones in PHT and vascular reactivity of mesenteric arterioles in rats. METHODS Cirrhosis and PHT were established by subcutaneous injection of carbon tetrachloride (CCl4) in both male and female integral and castrated rats (ovariectomized [OVX] in female rats, orchiectomy [ORX] in male rats). The third-order branch of the mensenteric artery was divided and used to measure vascular reactivity to vasoconstrictors. RESULTS No significant difference in portal pressure was observed between integral and castrated male PHT rats (15.2 ± 2.1 mmHg vs 16.7 ± 2.7 mmHg, P > 0.05). The portal pressure in integral female PHT rats was lower than that in OVX female PHT rats (12.7 ± 2.7 mmHg vs 16.5 ± 2.4 mmHg, P < 0.05). In PHT rats, the concentration response curves of the mesenteric arterioles to norepinephrine were shifted to the right, and the maximal responses (Emax) values were decreased and effective concentrations causing half maximum responses (EC50) values were increased, compared to those of non-PHT rats, both in male and female rats. Compared to non-PHT integral male rats, the sensitivity of the mesenteric arterioles of non-PHT ORX male rats to norepinephrine was decreased (P > 0.05). However, there was no difference between integral and ORX male rats with PHT. In integral female PHT rats, the concentration response curves were shifted to the left (P < 0.05), and the Emax values were increased and EC50 values were decreased compared to OVX female PHT rats. CONCLUSION Clear gender differences were observed in mesenteric vascular reactivity in CCl4-induced cirrhotic and PHT rats. Conservation of estrogen can retain the sensitivity of the mesenteric arterioles to vasoconstrictors and has a protective effect on splanchnic vascular function in PHT.

Chronic kidney disease (CKD) is often complicated by difficult-to-control hypertension, in part due to chronic overactivation of the sympathetic nervous system (SNS). CKD patients also exhibit a greater increase in arterial blood pressure for a given increase in sympathetic nerve activation, suggesting an augmented vasoconstrictive response to SNS activation (i.e., neurovascular transduction). One potential mechanism of increased sympathetic neurovascular transduction is heightened sensitivity of the vascular α1-adrenergic receptors (α1ARs), the major effectors of vasoconstriction in response to norepinephrine release at the sympathetic nerve terminals. Therefore, we hypothesized that patients with CKD have increased vascular α1AR sensitivity. We studied 32 patients with CKD stages III and IV (age 59.9 ± 1.3 yr) and 19 age-matched controls (CON, age 63.2 ± 1.6 yr). Using a linear variable differential transformer (LVDT), we measured change in venoconstriction in response to exponentially increasing doses of the selective α1AR agonist phenylephrine (PE) administered sequentially into a dorsal hand vein. Individual semilogarithmic PE dose-response curves were constructed for each participant to determine the PE dose at which 50% of maximum venoconstriction occurred (ED50), reflecting α1AR sensitivity. In support of our hypothesis, CKD patients had a lower PE ED50 than CON (CKD = 2.23 ± 0.11 vs. CON = 2.63 ± 0.20, P = 0.023), demonstrating increased vascular α1AR sensitivity. Additionally, CKD patients had a greater venoconstrictive capacity to PE than CON ( P = 0.015). Augmented α1AR sensitivity may contribute mechanistically to enhanced neurovascular transduction in CKD and may explain, in part, the greater blood pressure reactivity exhibited in these patients.

IntroductionVascular dysfunction due to reduced nitric oxide bioavailability plays an important role in the pathogenesis of sepsis. This meta-analysis examines evidence from published literature to evaluate whether in the adult population the presence/severity of sepsis is associated with impaired vasoreactivity.Material and methodsWe performed a search of the Medline, Scopus, and EMBASE databases to identify observational studies using measurement of reactive hyperaemia in adult patients with sepsis. After data extraction using predefined protocol, qualitative synthesis of findings was performed regarding consistency of findings between methods, evidence of association between vascular reactivity and severity of sepsis, multiple organ failure, and death. A meta-analyses of standardised mean differences in vasoreactivity between groups was performed, in which data were available for relevant outcomes.ResultsEighteen studies using four methods to measure vascular reactivity from a total of 466 were included in the analysis. The pooled standardised mean difference estimate showed that septic patients had less reactive hyperaemia than controls (–2.59, 95% CI: –3.46 to –1.72; p < 0.00001), and peak hyperaemic blood flow was lower in patients with sepsis than in the control group (SMD = –1.42, 95% CI: –2.14 to –0.70; p = 0.0001). The combined SMD between non survivors and survivors was –0.36 (95% CI: –0.67 to –0.06; p = 0.02) for reactive hyperaemia and –0.70 (95% CI: –1.13 to –0.27; p = 0.001) for peak hyperaemic blood flow.ConclusionsSeptic patients have attenuated vascular reactivity when compared to healthy volunteers. There are insufficient data indicating that these changes can identify patients at risk of worsening organ failure or death.

Objective To study whether vascular reactivity as assessed by the methods forearm blood flow (FBF) and postocclusive reactive hyperaemia (PRH) in the nail fold was related as a measure of endothelium-dependent vasodilation in the microcirculation. Methods Microvascular reactivity was assessed in forearm blood flow and in the nail fold by vital capillaroscopy of individual microvessels as postocclusive reactive hyperaemia. Vascular reactivity was assessed at baseline (n = 25) as well as after infusion of acetylcholine and of sodium nitroprusside (n = 13). We also performed a multivariate regression analysis to assess whether forearm blood flow or flow-mediated dilatation related to postocclusive reactive hyperaemia. Results This study showed a distinct microvascular response to both acetylcholine (endothelium-dependent vasodilation) and sodium nitroprusside (endothelium-independent vasodilation) during forearm blood flow assessment and postocclusive reactive hyperaemia assessment in the nail fold (n = 13). These changes were inversely related (r- = -0·57; P Conclusions Forearm blood flow was inversely correlated to postocclusive reactive hyperaemia. Postocclusive reactive hyperaemia was shortened after infusion with both acetylcholine and sodium nitroprusside. This occurred in parallel with the expected increase in forearm blood flow, conceivably reflecting that both methods can be used to assess endothelium-dependent vasodilation in the microcirculation.

The results of treatment of adhesive intestinal obstruction with laparoscopic adhesion and intestinal sympathectomy based on the concept of congenital or acquired propensity to pathological adhesion due to individual vascular reactivity, which creates prolonged peritoneal ischemia and, as a result, chronic inflammatory response to peritoneal alteration are presented. The purpose of the study was to study the effectiveness of the use of laparoscopic adhesion in combination with the implementation of left ventricular sympathectomy for the prevention and treatment of pathological adhesion. For the analysis of the results, clinical methods of research were used, namely: terms of restoration of the peristalsis and stool, the severity of the pain syndrome, duration of hospitalization. The method has been tested in clinical conditions for 58 patients after experimental study. As a control, the results of the treatment of 10 patients with laparotomic access without carrying out intestinal sympathectomy are analyzed. The obtained results testify to the effectiveness of the proposed method of prevention and treatment of pathological adhesion by the laparoscopic method.

Breath holding (BH) is a viable vasodilatory stimulus for calculating functional MRI-derived cerebral vascular reactivity (CVR). The BH technique suffers from reduced repeatability compared with gas inhalation techniques; however, extra equipment is needed to perform gas inhalation techniques, and this equipment is not available at all institutions. This study aimed to determine the sensitivity and repeatability of BH activation and CVR using a multiband multi-echo simultaneous arterial spin labelling/blood oxygenation level dependent (ASL/BOLD) sequence. Whole-brain images were acquired in 14 volunteers. Ten subjects returned for repeat imaging. Each subject performed four cycles of 16 s BH on expiration interleaved with paced breathing. Following standard preprocessing, the echoes were combined using a T2*-weighted approach. BOLD and ASL BH activation was computed, and CVR was then determined as the percent signal change related to the activation. The “M” parameter from the Davis Model was also computed by incorporating the ASL signal. Our results showed higher BH activation strength, volume, and repeatability for the combined multi-echo (MEC) data compared with the single-echo data. MEC CVR also had higher repeatability, sensitivity, specificity, and reliability compared with the single-echo BOLD data. These data support the usefulness of an MBME ASL/BOLD acquisition for BH CVR and M measurements.

Clinical studies have shown that obesity negatively impacts large arteries’ function. We reported that rats exposed to maternal separation (MatSep), a model of early life stress, display enhanced angiotensin II (ANG II)-induced vasoconstriction in aortic rings cleaned of perivascular adipose tissue (PVAT) under normal diet (ND) conditions. We hypothesized that exposure to MatSep promotes a greater loss of PVAT-mediated protective effects on vascular function and loss of blood pressure (BP) rhythm in rats fed a high-fat diet (HFD) when compared with controls. MatSep was performed in male Wistar-Kyoto rats from days 2 to 14 of life. Normally reared littermates served as controls. On ND, aortic rings from MatSep rats with PVAT removed showed increased ANG II-mediated vasoconstriction versus controls; however, rings from MatSep rats with intact PVAT displayed blunted constriction. This effect was exacerbated by an HFD in both groups; however, the anticontractile effect of PVAT was greater in MatSep rats. Acetylcholine-induced relaxation was similar in MatSep and control rats fed an ND, regardless of the presence of PVAT. HFD impaired aortic relaxation in rings without PVAT from MatSep rats, whereas the presence of PVAT improved relaxation in both groups. On an HFD, immunolocalization of vascular smooth muscle-derived ANG-(1–7) and PVAT-derived adiponectin abundances were increased in MatSep. In rats fed an HFD, 24-h BP and BP rhythms were similar between groups. In summary, MatSep enhanced the ability of PVAT to blunt the heightened ANG II-induced vasoconstriction and endothelial dysfunction in rats fed an HFD. This protective effect may be mediated via the upregulation of vasoprotective factors within the adipovascular axis.

Extracts of ginseng species show antihyperglycemic activity. We evaluated the inhibitory effects of diabetic complications for Korean Red Ginseng (KRG), which is enriched in ginsenosides using Otsuka Long-Evans Tokushima Fatty (OLETF) rats. The animals were divided into one of four groups (n = 6∼9): Long–Evans–Tokushima–Otsuka rats (control rats), OLETF rats, rats given 200 mg/kg KRG, and rats given 400 mg/kg KRG. We examined the protective potential of KRG against type 2 diabetic illnesses. The results exhibited that KRG showed significant antihyperglycemic and antioxidative effects in KRG-treated OLETF rats. And, our results proposed the amelioration of cardiac function through normalized ejection fraction, fractional shortening, and vascular reactivity. Furthermore, histopathological abnormalities in the OLETF rats were prevented by KRG treatment. Keywords: hemodynamics, Korean Red Ginseng, Protection, Type 2 diabetes, vesicular function

Covid-19 infection may be associated with a higher incidence developing cardiovascular complications, however, the underlying mechanisms contributing to cardiovascular complications are largely unknown, while endothelial cell damage may be present. We want to report a 24-year-old woman with Covid-19 infection who had undergone measurements of vascular reactivity and arterial stiffness, including flow-mediated dilation (FMD), nitroglycerin-mediated dilation (NMD), aortic pulse wave velocity (PWV), augmentation index and carotid intima-media-thickness (cIMT) at the time when Covid-19 was diagnosed. Reduced FMD of 0.0% and NMD of 15.5% were observed, while PWV (5.9 m/s), Aix (27%) and cIMT with 0.4 mm of both common carotid arteries were unremarkable. Repeated measurements of FMD, NMD, PWV, Aix, and cIMT 6 weeks after Covid-19 infection revealed persistently reduced FMD (0.0%), while NMD (17.24%), PWV (5.6 m/s) and augmentation index (13%) ameliorated. This case suggests potential impact of Covid-19 infection on endothelial function, also in young Covid-19 patients without any co-morbidity.

Introduction: Heart preservation benefits cardiac performance after operations decreasing morbidity but the contribution of the vascular reactivity has been neglected. Objective: We evaluated whether cardioprotective solutions, Krebs-Henseleit (KH), Bretschneider-HTK (BHTK), St. Thomas No. 1 (STH-1), and Celsior (CEL), affect vascular reactivity. Methods: Aortic rings from Wistar rats were used in two protocols. First, the rings were exposed to BHTK, STH-1 or CEL for 1 hour of hypoxia at 37 °C. Second, the rings were exposed to 10 °C or 20 °C for 1 hour under hypoxia. After treatment, the rings were immersed in KH at 37 °C, endothelial integrity was tested and concentration-response curves to phenylephrine were performed. Results: In the first protocol, the solutions did not damage the endothelium; CEL and BHTK reduced KCl-induced contractions but not STH-1; only CEL and BHTK reduced vascular reactivity; there was a positive correlation between Rmax and KCl concentration. At 20 °C, 1 hour under hypoxia, the solutions produced similar KCl-induced contractions without endothelial damage. CEL, BHTK and STH-1 decreased vascular reactivity. At 10 °C, STH-1 increased reactivity but CEL and BHTK decreased. After 1 hour under hypoxia in CEL or BHTK solutions, reactivity was similar at different temperatures. At 20 °C, endothelial damage after exposure to STH-1 produced more vasoconstriction than CEL and BHTK. However, at 10 °C, endothelial damage after CEL and BHTK exposure elicited more vasoconstriction while STH-1 showed a small vasoconstrictor response, suggesting endothelial damage. Conclusion: STH-1 decreased reactivity at 20 °C and increased at 10 °C. CEL promoted greater endothelial modulation at 10 °C than at 20 °C, while STH-1 promoted higher modulation at 20 °C than at 10 °C. Vascular tone was reduced by CEL and BHTK exposure, also depending on the KCl concentration.

Background Visual and molecular changes occurring upon aging are rather well characterized. Still, aging signs show great significant inter-individual variations, and little is known concerning the link between perceived age and cutaneous microcirculation. Materials and methods To investigate this point, we recruited Caucasian women in their mid-50's to mid-70's and subsampled women looking older or younger than their age. We studied their facial skin color, as well as their microvascular reactivity to local heating assessed in the forearm skin. We also used skin biopsies from some of these women for gene expression or immunohistochemical analysis. Results Clinical and instrumental analysis of skin color revealed that subjects who look 5 years younger differ only by a higher glowing complexion. Our most striking result is that subjects looking 5 years younger than their age present a higher microcirculation reactivity in forearm skin. Transcriptome comparison of skin samples from women looking older or younger than their age revealed 123 annotated transcripts differentially expressed, among which MYL9 relates to microcirculation. MYL9 is downregulated in the group of women looking younger than their real age. Microscopy shows that the labeling of MYL9 and CD31 are altered and heterogeneous with age, as is the morphology of microvessels. Conclusion Therefore, assessing generalized vascular reactivity in non-photo-exposed skin to focus on the intrinsic aging allows subtle discrimination of perceived age within elderly healthy subjects.

In patients with sickle cell disease (SCD), cerebral blood flow (CBF) is elevated to counteract anemia and maintain oxygen supply to the brain. This may exhaust the vasodilating capacity of the vessels, possibly increasing the risk of silent cerebral infarctions (SCI). To further investigate cerebrovascular hemodynamics in SCD patients, we assessed CBF, arterial transit time (ATT), cerebrovascular reactivity of CBF and ATT (CVRCBF and CVRATT) and oxygen delivery in patients with different forms of SCD and matched healthy controls. We analyzed data of 52 patients with severe SCD (HbSS and HbSβ0-thal), 20 patients with mild SCD (HbSC and HbSβ+-thal) and 10 healthy matched controls (HbAA and HbAS). Time-encoded arterial spin labeling (ASL) scans were performed before and after a vasodilatory challenge using acetazolamide (ACZ). To identify predictors of CBF and ATT after vasodilation, regression analyses were performed. Oxygen delivery was calculated and associated with hemoglobin and fetal hemoglobin (HbF) levels. At baseline, severe SCD patients showed significantly higher CBF and lower ATT compared to both the mild SCD patients and healthy controls. As CBFpostACZ was linearly related to CBFpreACZ, CVRCBF decreased with disease severity. CVRATT was also significantly affected in severe SCD patients compared to mild SCD patients and healthy controls. Considering all groups, women showed higher CBFpostACZ than men (p < 0.01) independent of baseline CBF. Subsequently, post ACZ oxygen delivery was also higher in women (p < 0.05). Baseline, but not post ACZ, GM oxygen delivery increased with HbF levels. Our data showed that baseline CBF and ATT and CVRCBF and CVRATT are most affected in severe SCD patients and to a lesser extent in patients with milder forms of SCD compared to healthy controls. Cerebrovascular vasoreactivity was mainly determined by baseline CBF, sex and HbF levels. The higher vascular reactivity observed in women could be related to their lower SCI prevalence, which remains an area of future work. Beneficial effects of HbF on oxygen delivery reflect changes in oxygen dissociation affinity from hemoglobin and were limited to baseline conditions suggesting that high HbF levels do not protect the brain upon a hemodynamic challenge, despite its positive effect on hemolysis.