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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.

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.

Background and aims The new coronavirus disease (Covid-19) is a systemic disease. Mounting evidence depict signs and symptoms involving multiple organs, most of which supported by pathological data. A plausible link to these manifestations is vascular and endothelial dysfunction/damage. However, much of the current knowledge relies on opinion and incipient evidence. We aim to objectively appraise current evidence on the association between Covid-19 and vascular disease, specifically endotheliitis and vasculitis. Methods Two researchers independently entered the search terms Covid-19 OR SARS-CoV-2 AND vasculitis, endotheliitis OR endothelium in the following online platforms: MedRxiv and LitCovid (PubMed). The search period was set from November 1, 2019 to August 28, 2020. Manuscripts with unavailable full texts, not in English, mainly on pre-clinical data, presenting only study designs or not directly related to the topics of this review were excluded. Retrospective and prospective studies, especially longitudinal ones, were given priority to the purpose of this review. Since there was paucity of prospective controlled evidence, case reports/series were also considered. Results A total of 318 manuscripts were initially found. Sixty-seven (21%) were excluded: 59 (18.5%) met exclusion criteria and 8 (2.5%) were duplicates. One hundred and forty-two manuscripts (44,6%) did not provide original data and were also excluded: 35 (11%) were comments, 108 (33.9%) reviews; 1 (0.3%) position paper. One hundred and seven (33.6%) studies were considered for the present scoping review: 81 (25,5%) case reports/series; 18 (5.7%) prospective; 8 (2.5%) retrospective. Viral inclusions in endothelial cells, mononuclear cell infiltrates in the intima of small vessels and markers of endothelial cell apoptosis were demonstrated. Specificities of Covid-19 may lead to diverse vascular manifestations in different levels of the vascular bed. Conclusions Evidence indicates that Covid-19 targets vasculature and endothelium. However, high quality data is still lacking and studies with prospective designs and appropriately matched controls are needed., Graphical abstract Mechanisms of SARS-CoV-2-related vasculitis/endotheliitis. Covid-19 may affect the endothelium and smooth muscle cells of the arterial and venous wall at different levels and through multiple ways, namely: inflammation/immune response, hypercoagulability and increased vascular reactivity. ACE-2: angiotensin-converting enzyme 2; Angpt: angiopoietin; CEC: circulating endothelial cells; CRP: C-reactive protein; DIC: disseminated intravascular coagulopathy; IFN-1: interferon type 1; IL: interleukin; MCP-1: monocyte chemotactic protein-1; NETs: neutrophil extracellular traps; NO: nitric oxide; sVCAM-1: soluble vascular cell adhesion molecule-1; sVCAM-1: soluble vascular cell adhesion molecule-1; TMA: thrombotic microangiopathy; TNF- α: tumor necrosis factor – α; VAP-1: vascular adhesion protein-1.Image 1

Objective The balance between nitric oxide (NO)-sensitive and -insensitive forms of soluble guanylate cyclase (sGC) has been demonstrated to be disrupted in certain lifestyle-related diseases. However, it remains unclear whether type 2 diabetes results in a shift of sGC to the NO-insensitive form. This study addressed this issue in the human blood vessel. Methods Internal thoracic arteries were obtained from patients undergoing coronary artery bypass grafting. Helically cut strips of the arteries were suspended in organ chambers, and relaxant responses to nitroglycerin (NO-sensitive sGC stimulant) and BAY 60-2770 (NO-insensitive sGC stimulant) were assessed. Results The patients were divided into two groups according to the presence of type 2 diabetes (HbA1c: 7.0 ± 0.3%) or its absence (HbA1c: 5.6 ± 0.1%). Nitroglycerin-induced relaxation was not different in the arteries obtained from type 2 diabetic and non-diabetic patients. In addition, the relaxant response to BAY 60-2770 in type 2 diabetics was comparable to that observed in non-diabetics. Although the patients enrolled often had vascular risk factors other than type 2 diabetes, the relaxant responses were still in the same range in a comparison based on the number of risk factors. However, in separate experiments, the relaxant response to nitroglycerin was attenuated by pre-incubation of the arteries with ODQ (sGC imbalance inducer), whereas the relaxant response to BAY-60-2770 was augmented. Conclusions These findings suggest that type 2 diabetes does not affect the balance between NO-sensitive and -insensitive sGC in human internal thoracic artery grafts.

International audience; ObjectiveTo evaluate whether active immunization producing β1- or β3-antibodies (β1-ABs and β3-ABs) detected in sera of patients with dilated cardiomyopathies has deleterious effects on vascular reactivity in Lewis rat thoracic aorta (TA) and small mesenteric arteries (SMA).Design and methodLewis rats were immunized for 6months with peptidic sequences corresponding to the second extracellular loop of β1- and β3-adrenoceptors (ARs). During the immunization, systolic blood pressure (SBP) was monitored using the tail cuff method. The vascular reactivity of immunized rats was assessed by ex vivo studies on SMA and TA using various β-AR agonists, phenylephrine and KCl.ResultsThe immunizations producing functional β1-ABs and β3-ABs did not affect the SBP. However, in TA from β1-AR-immunized rats, the relaxations mediated by dobutamine and salbutamol were significantly impaired in comparison with adjuvant rats whereas nebivolol-induced relaxation was not modified. Moreover, phenylephrine and KCl-mediated contractions were enhanced in these rats. In contrast, immunization with β3-AR peptide led to the increase of relaxations induced by dobutamine in TA but did not change those induced by salbutamol and nebivolol. Surprisingly, in SMA from both rats immunized with β1- or β3-peptides, relaxations induced by the various β-agonists were not changed whereas phenylephrine and KCl-mediated contractions were impaired.ConclusionsOur study shows that β1- and β3-ABs can affect vascular reactivity. β1-ABs would have a pathogenic action whereas β3-ABs would have a beneficial effect on aorta reactivity.Array( [0] => public://js/js_NhB8QqEMkIRnGegV_fyHSoTNS4QcuYAxmtYDZC610gE.js.gz : fichier présent sur le disque mais absent dans la base de données [1] => public://js/js_YqvqIXMHR_JA_6L7V5VgwgrhCDVtmWC_wCWsaINFQtk.js : fichier présent sur le disque mais absent dans la base de données [2] => public://js/js_YqvqIXMHR_JA_6L7V5VgwgrhCDVtmWC_wCWsaINFQtk.js.gz : fichier présent sur le disque mais absent dans la base de données [3] => public://js/js_NhB8QqEMkIRnGegV_fyHSoTNS4QcuYAxmtYDZC610gE.js : fichier présent sur le disque mais absent dans la base de données)

Growth hormone deficiency (GHD) in adulthood is associated with an increased risk of developing adverse cardiovascular events and with reduced life expectancy. Cardiovascular and metabolic abnormalities have so far been evaluated only in a small number of children with GHD and adolescents. In this article we review these abnormalities and their underlying mechanisms and discuss the beneficial effect of growth hormone treatment in subjects with GHD.

Functional MRI (fMRI) is well-established for the study of brain function in healthy populations, although its clinical application has proven more challenging. Specifically, cerebrovascular reactivity (CVR), which allows the assessment of the vascular response that serves as the basis for fMRI, has been shown to be reduced in healthy aging as well as in a range of diseases, including chronic stroke. However, the timing of when this occurs relative to the stroke event is unclear. We used a breath-hold fMRI task to evaluate CVR across gray matter in a group of acute stroke patients (, Highlights • Breath-holding can be used to assess the validity of fMRI in stroke patients. • Vascular reactivity, estimated by breath-hold fMRI, was greatest in young controls. • Acute stroke patients and age-matched controls had similar vascular reactivity. • Modeling the breath-hold response on an individual basis can improve results.

Ticagrelor has shown superiority compared with clopidogrel in reducing cardiovascular events [(1)][1]. Although some of the clinical benefits of ticagrelor may simply reflect its potency in inhibiting platelet aggregation, the action of this drug on blood vessels may also play a role. Ticagrelor

The present study evaluates the effect of fish protein hydrolysate (FPH) ingestion on macro- and microvascular endothelial function and blood pressure (BP) in subjects at high risk of cardiovascular disease (CVD). In a randomized, placebo-controlled, double-blind, crossover design, twelve individuals ingested a single dose of FPH or PLA. Flow-mediated dilation (FMD) was used to evaluate the macrovascular endothelial function and near-infrared spectroscopy-derived muscle O2 desaturation and resaturation parameters were used to evaluate muscle O2 extraction and microvascular reactivity, respectively, during arterial occlusion test. FMD and muscle O2 saturation were assessed at 60−70 min after the nutritional intervention. A significant improvement in FMD (P 0.05). The data demonstrated that FPH ingestion acutely improved FMD and muscle O2 desaturation and resaturation parameters in individuals at high risk of CVD. Additionally, no changes in BP were observed.

Perivascular adipose tissue (PVAT) is recognized as a paracrine organ that controls vascular function. One of the early data demonstrated PVAT from male Sprague-Dawley rats altered aortic vascular reactivity [1]. Subsequent studies have suggested PVAT mediated vascular reactivity is impaired in a variety of vascular beds with animal models of metabolic syndrome [2]. Findings in these experimental animals are generally reported by only male data. Here we report the new data on the effects of PVAT on the aortic reactivity of female lean zucker rats (LZR) and obese zucker rats (OZR). The data presented here is related to a recent manuscript entitled “Aortic dysfunction in metabolic syndrome mediated by perivascular adipose tissue TNFα- and NOX2-dependent pathway” [3] which demonstrated PVAT from male obese Zucker rats (OZR) impaired endothelial function of aorta which is associated with altered PVAT inflammatory signaling. Keywords: Female Zucker rats, Perivascular adipose tissue, Vascular reactivity, Inflammation

Aims: The aim of this study was to evaluate the effects of acute hypobaric hypoxia (HH) on vascular reactivity and biochemical markers associated with endothelial function (EF). Main methods: Ten healthy subjects were exposed to a simulated altitude of 4,000 meters above sea level for 4 hours in a hypobaric chamber. Vascular reactivity was measured by the flow-mediated vasodilatation (FMVD) test. Endothelin-1, high sensitive-C reactive protein (hsCRP), vascular cell adhesion molecule 1, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), paraoxonase and adiponectin levels, and FMVD were evaluated before and after the exposure. Key findings: Subjects were young (age: 32±6 years), lean [body mass index: 23.9±2.0kg/m(2), waist circumference: 77(IQR: 72-80) cm], and presented normal clinical and biochemical parameters. No significant changes were evidenced in FMVD in response to HH (pre: 0.45 (0.20-0.70) vs. during: 0.50 (0.20-1.22) mm; p=0.594). On the other hand, endothelin-1 (+54%, p

Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), has effects beyond its antidepressant properties, altering, e.g., mechanisms involved in blood pressure and vasomotor tone control. Although many studies have addressed the acute impact of fluoxetine on the cardiovascular system, there is a paucity of information on the chronic vascular effects of this SSRI. We tested the hypothesis that chronic fluoxetine treatment enhances the vascular reactivity to vasodilator stimuli by increasing nitric oxide (NO) signaling and activation of potassium (K+) channels. Wistar rats were divided into two groups: (I) vehicle (water for 21 days) or (II) chronic fluoxetine (10mg/kg/day in the drinking water for 21 days). Fluoxetine treatment increased endothelium-dependent and independent vasorelaxation (analyzed by mesenteric resistance arteries reactivity) as well as constitutive NO synthase (NOS) activity, phosphorylation of eNOS at Serine1177 and NO production, determined by western blot and fluorescence. On the other hand, fluoxetine treatment did not alter vascular expression of neuronal and inducible NOS or guanylyl cyclase (GC). Arteries from fluoxetine-treated rats exhibited increased relaxation to pinacidil. Increased acetylcholine vasorelaxation was abolished by a calcium-activated K+ channel (KCa) blocker, but not by an inhibitor of KATP channels. On the other hand, vascular responses to Bay 41-2272 and 8-bromo-cGMP were similar between the groups. In conclusion, chronic fluoxetine treatment increases endothelium-dependent and independent relaxation of mesenteric resistance arteries by mechanisms that involve increased eNOS activity, NO generation, and KCa channels activation. These effects may contribute to the cardiovascular effects associated with chronic fluoxetine treatment.

Postischemic angiogenesis is an important recovery mechanism. Both arteries and veins are upregulated during angiogenesis, but eventually there are more angiogenic veins than arteries in terms of number and length. It is critical to understand how the veins are modulated after ischemia and then transitioned into angiogenic vessels during the proangiogenic stage to finally serve as a restorative strength to the injured area. Using a rat model of transient focal cerebral ischemia, the hypercapnic blood oxygen level-dependent (BOLD) response was used to evaluate vascular reactivity, while the hyperoxic BOLD and tissue oxygen level-dependent (TOLD) responses were used to evaluate the vascular functionality at 1, 3, and 7 days after ischemia. Vessel-like venous signals appeared on R2* maps on days 3 and 7, but not on day 1. The large hypercapnic BOLD responses on days 3 and 7 indicated that these areas have high vascular reactivity. The temporal correlation between vascular reactivity and the immunoreactivity to desmin and VEGF further indicates that the integrity of vascular reactivity is associated with the pericyte coverage as regulated by the VEGF level. Vascular functionality remained low on days 1, 3, and 7, as reflected by the small hyperoxic BOLD and large hyperoxic TOLD responses, indicating the low oxygen consumption of the ischemic tissues. These functional changes in proangiogenic veins may be critical for angiogenesis.

FMRI BOLD responses to changes in neural activity are influenced by the reactivity of the vasculature. By complementing a task-related BOLD acquisition with a vascular reactivity measure obtained through breath-holding or hypercapnia, this unwanted variance can be statistically reduced in the BOLD responses of interest. Recently, it has been suggested that vascular reactivity can also be estimated using a resting state scan.\ud \ud This study aimed to compare three breath-hold based analysis approaches (block design, sine–cosine regressor and CO2 regressor) and a resting state approach (CO2 regressor) to measure vascular reactivity. We tested BOLD variance explained by the model and repeatability of the measures. Fifteen healthy participants underwent a breath-hold task and a resting state scan with end-tidal CO2 being recorded during both. Vascular reactivity was defined as CO2-related BOLD percent signal change/mm Hg change in CO2.\ud \ud Maps and regional vascular reactivity estimates showed high repeatability when the breath-hold task was used. Repeatability and variance explained by the CO2 trace regressor were lower for the resting state data based approach, which resulted in highly variable measures of vascular reactivity.\ud \ud We conclude that breath-hold based vascular reactivity estimations are more repeatable than resting-based estimates, and that there are limitations with replacing breath-hold scans by resting state scans for vascular reactivity assessment.

Epidemiological studies have established that radiation from a number of terrestrial sources increases the risk of atherosclerosis. The accelerated heavy ions in the galacto-cosmic radiation (GCR) that astronauts will encounter on in space, however, interact very differently with tissues than most types of terrestrial radiation, so the health consequences of exposure on deep-space missions are not clear. We demonstrated earlier that 56Fe, an important component of cosmic radiation, accelerates atherosclerotic plaque development. In the present study, we examined an earlier, pro-atherogenic event that might be predictive of later atherosclerotic disease. Decreased endothelium-dependent vasodilation is a prominent manifestation of vascular dysfunction that is thought to predispose humans to the development of structural vascular changes that precede the development of atherosclerotic plaques. To test the effect of heavy-ion radiation on endothelium-dependent vasodilation, we used the same ApoE–/– mouse model in which we previously demonstrated the pro-atherogenic effect of 56Fe on plaque development. Ten week old male ApoE mice (an age at which there is little atherosclerotic plaque in the descending aorta) were exposed to 2.6 Gy 56Fe. The mice were then fed a normal diet and housed under standard conditions. At 4–5 weeks post-irradiation, aortic rings were isolated and endothelial-dependent relaxation was measured. Relaxation in response to acetylcholine was significantly impaired in irradiated mice compared to age-matched, un-irradiated mice. This decrease in vascular reactivity following 56Fe irradiation occurred eight weeks prior to the development of statistically significant exacerbation of aortic plaque formation and may contribute to the formation of later atherosclerotic lesions.

Chronic exposure to low lead concentration produces hypertension; however, the underlying mechanisms remain unclear. We analyzed the role of oxidative stress, cyclooxygenase-2-dependent pathways and MAPK in the vascular alterations induced by chronic lead exposure. Aortas from lead-treated Wistar rats (1st dose: 10 μg/100 g; subsequent doses: 0.125 μg/100 g, intramuscular, 30 days) and cultured aortic vascular smooth muscle cells (VSMCs) from Sprague Dawley rats stimulated with lead (20 μg/dL) were used. Lead blood levels of treated rats attained 21.7 ± 2.38 μg/dL. Lead exposure increased systolic blood pressure and aortic ring contractile response to phenylephrine, reduced acetylcholine-induced relaxation and did not affect sodium nitroprusside relaxation. Endothelium removal and L-NAME left-shifted the response to phenylephrine more in untreated than in lead-treated rats. Apocynin and indomethacin decreased more the response to phenylephrine in treated than in untreated rats. Aortic protein expression of gp91(phox), Cu/Zn-SOD, Mn-SOD and COX-2 increased after lead exposure. In cultured VSMCs lead 1) increased superoxide anion production, NADPH oxidase activity and gene and/or protein levels of NOX-1, NOX-4, Mn-SOD, EC-SOD and COX-2 and 2) activated ERK1/2 and p38 MAPK. Both antioxidants and COX-2 inhibitors normalized superoxide anion production, NADPH oxidase activity and mRNA levels of NOX-1, NOX-4 and COX-2. Blockade of the ERK1/2 and p38 signaling pathways abolished lead-induced NOX-1, NOX-4 and COX-2 expression. Results show that lead activation of the MAPK signaling pathways activates inflammatory proteins such as NADPH oxidase and COX-2, suggesting a reciprocal interplay and contribution to vascular dysfunction as an underlying mechanisms for lead-induced hypertension, This work was supported by MINECO (SAF2012-36400), ISCIII 7 (RD12/0042/0024), PRONEX-CNPq/FAPES (48511935/2009). MRS was a 8 fellow of CAPES and CNPq. AMB was supported by the Ramon y Cajal 9 Program (RyC2010-06473).

Aim In previous reports both microcirculatory alterations and impaired vascular reactivity have been described in post cardiac arrest patients treated with mild therapeutic hypothermia. As of now it is unknown whether these alterations are related to the temperature management or to the cardiac arrest itself. Aim of the present study was to investigate the potential difference in microcirculatory alterations and vascular reactivity in comatose patients after out of hospital cardiac arrest treated with target temperature management of 33°C (TTM33) in comparison to patients treated with 36°C (TTM36). Methods Our study was designed as a predefined substudy of the open label randomized controlled TTM trial in 2 Dutch mixed ICU's. Sublingual microvascular flow index (MFI) was assessed by Side Stream Darkfield imaging and vascular reactivity at the thenar region of the hand by near infrared spectroscopy. Variables, including systemic hemodynamics were recorded at start study (T1), after 12h (T2) and after 24h (T3). Results 22 patients were included, 13 in TTM33 and 9 in TTM36. At T1 MFI between groups did not differ significantly (1.08 [0.4–1.9] versus 1.67 [0.7–2.4] respectively, p =0.59). The difference between groups remained insignificant over time. At T1 tissue oxygenation (StO 2 ) was significantly lower in TTM36 in comparison to TTM33: (44.6±15.8 versus 58.9±13.5, p =0.03). Over time this difference between groups disappeared. However, vascular reactivity, expressed as the descending and ascending slope of StO 2 after a standardized ischemic occlusion test was similar between groups. Conclusions In this relatively small sample size study microcirculatory blood flow and vascular reactivity did not differ nor change between TTM33 and TTM36.

The association between the consumption of pure (100%) fruit juice (PFJ) and human health is uncertain. The current review summarizes data published between 1995 and 2012 related to PFJ with a focus on juices that are widely available and studied in forms representing native juice without supplemental nutrients or enhanced phytochemical content. The effects of apple, cranberry, grape, grapefruit, orange, and pomegranate PFJ intake on outcomes linked to cancer, cardiovascular disease, cognition, hypertension, inflammation, oxidation, platelet function, urinary tract infection, and vascular reactivity are reviewed. Implications for bodyweight regulation are also addressed. The collective data are provocative although challenges and unanswered questions remain. There are many plausible mechanisms by which PFJ might be protective, and investigation of its effects on human health and disease prevention must remain an active area of research.

Resume But de l’etude Analyser les modifications de la reactivite vasculaire en reponse a des protocoles d’immunisation par des antigenes correspondants a la seconde boucle extracellulaire des recepteurs adrenergiques (RA) –β3 ou –β1 et 3. Methodes Des rats Lewis ont ete immunises pendant 3 mois avec un peptide correspondant a la seconde boucle extracellulaire des RA–β3 ou –β1 et 3. Les anticorps anti-RA–β (AC–RA–β) produits ont ete titres par Elisa et purifies en utilisant le kit « Proteus Protein G ». Leur fonctionnalite a ensuite ete testee dans des cardiomyocytes ventriculaires isoles chez le lapin. Des anneaux d’aorte et d’artere mesenterique isoles ont ete montes dans des cuves a organes isoles et precontractes a la phenylephrine. Puis, des courbes de relaxation ont ete realisees. Resultats Le SR58611A (agoniste des RA–β3) (10 nM) et les AC–RA–β3 purifies (25 μg/mL) induisent une diminution du pourcentage de raccourcissement cellulaire (respectivement −39,6 ± 4,4 % [n = 11] et −18,5 ± 3,9 % [n = 10]) des cardiomyocytes isoles. Cette diminution est inhibee lorsque les cardiomyocytes sont preincubes avec le L–748337 (1 μM), un antagoniste selectif des RA–β3 (p Conclusion Ces resultats montrent pour la premiere fois que les AC–RA–β3 exercent un effet agoniste β3– adrenergique. Ils n’auraient pas d’action pathogene vasculaire mais compenseraient la dysfonction endotheliale provoquee par les AC–RA–β1.

This brief review of magnetic resonance susceptometry summarizes the methods conceived in the authors' laboratory during the past several years. This article shows how venous oxygen saturation is quantified in large draining veins by field mapping and how this information, in concert with simultaneous measurement of cerebral blood flow, yields cerebral metabolic rate of oxygen, the brain's rate of oxygen consumption. The accuracy of this model-based approach in which the blood vessel is approximated as a long, straight cylinder, for which an analytical solution for the induced field exists, is discussed. It is shown that the approach is remarkably robust, allowing for time-resolved quantification of whole-brain metabolism at rest and in response to stimuli, thereby providing detailed information on cerebral physiology in health and disease not previously amenable by noninvasive methods.

A high salt diet is associated with reduced activity of the renin–angiotensin–aldosterone system (RAAS). However, normotensive rats exposed to high sodium do not show changes in systemic arterial pressure. We hypothesized that, despite the reduced circulating amounts of angiotensin II induced by a high salt diet, the cardiovascular system's reactivity to angiotensin II is increased in vivo, contributing to maintain arterial pressure at normal levels. Male Wistar rats received chow containing 0.27% (control), 2%, 4%, or 8% NaCl for six weeks. The high-sodium diet did not lead to changes in arterial pressure, although plasma levels of angiotensin II and aldosterone were reduced in the 4% and 8% NaCl groups. The 4% and 8% NaCl groups showed enhanced pressor responses to angiotensin I and II, accompanied by unchanged and increased angiotensin-converting enzyme activity, respectively. The 4% NaCl group showed increased expression of angiotensin II type 1 receptors and reduced expression of angiotensin II type 2 receptors in the aorta. In addition, the hypotensive effect of losartan was reduced in both 4% and 8% NaCl groups. In conclusion these results explain, at least in part, why the systemic arterial pressure is maintained at normal levels in non-salt sensitive and healthy rats exposed to a high salt diet, when the functionality of RAAS appears to be blunted, as well as suggest that angiotensin II has a crucial role in the vascular dysfunction associated with high salt intake, even in the absence of hypertension.

The study by Ohyama et al. [(1)][1] rigorously confirms the strict relationship between inflammation and coronary vasomotion. We have 3 comments. First, the results intriguingly suggested that vascular reactivity could play as one of the possible pathogenetic links between inflammation and vascular

Pulmonary arterial hypertension (PAH) is associated with refractory vasoconstriction and impaired NO-mediated vasodilatation of the pulmonary vasculature. Vascular tone is regulated by light chain (LC) phosphorylation of both nonmuscle (NM) and smooth muscle (SM) myosins, which are determined by the activities of MLC kinase and MLC phosphatase. Further, NO mediated vasodilatation requires the expression of a leucine zipper positive (LZ+) isoform of the myosin targeting subunit (MYPT1) of MLC phosphatase. The objective of this study was to define contractile protein expression in the pulmonary arterial vasculature and vascular reactivity in PAH. In severe PAH, compared to controls, relative LZ+MYPT1 expression was decreased (100 ± 14% vs. 60 ± 6%, p

The aim of this study was to evaluate isometric muscle contraction (handgrip) changes on key elements of cardiac afterload, before and after raloxifene administration in postmenopausal women.12 postmenopausal and 12 fertile women were studied. Postmenopausal women underwent raloxifene administration (60 mg/day for 30 days). We evaluated vascular reactivity in superficial palmar arterial arch during handgrip in postmenopausal women before and after (M+R) drug administration, and in controls. Blood flow was higher after raloxifene administration (p0.05). Mean arterial pressure (MAP)/mean arterial flow (Fmed) and arterial pulse pressure (APP)/systolic maximum arterial flow (Fmax syst) were lower after raloxifene administration (p0.001). Systolic blood pressure (SBP)/R-R ratio was higher in postmenopausal women than in the controls and M+R (p0.01). End-handgrip systolic and diastolic blood pressure were higher in patients before raloxifene administration than in controls (p0.001); diastolic and mean arterial pressure reduced after raloxifene administration (p0.001). End-effort APP/Fmax syst-ratio before treatment was higher than baseline (p0.05). Controls and no-treated patients showed a MAP/Fmed ratio at end-handgrip higher than M+R group and rest (p0.05). Handgrip reduced R-R interval and increased SBP/R-R ratio were shown in all groups (p0.05).Raloxifene reduced the vascular effects of isometric muscle contraction by modulating the vasomotor tone of peripheral vessels in relation to exercise.

Resume Les agonistes alpha-2 adrenergiques (« agonistes alpha-2 ») presentent de multiples effets pharmacodynamiques : sedation dite « eveillable » ( rousable sedation ), diminution de l’incidence du syndrome confusionnel en reanimation, preservation du controle respiratoire (neurogenese respiratoire), diminution de la consommation d’oxygene, diminution de l’impedance arterielle systemique et pulmonaire, amelioration de la performance systolique et diastolique du ventricule gauche, preservation de la reactivite vasculaire aux catecholamines exogenes, preservation de l’activite baroreflexe vasomotrice avec point de consigne en pression plus faible, fonction renale preservee, diminution du catabolisme proteique. Ces effets pharmacodynamiques, potentiellement interessants en reanimation, expliquent l’interet porte aux agonistes alpha-2 pour la sedation en reanimation. Toutefois, la place exacte des agonistes alpha-2 en sedation de reanimation reste a determiner. Compte tenu de la paucite d’essais randomises multicentriques en double insu, cette analyse, non exhaustive, de la litterature a pour objectif de presenter l’utilisation potentielle des agonistes alpha-2 comme sedatifs de premiere intention en reanimation. Un protocole d’utilisation de ces molecules est propose.

Resume Objectif Evaluer l’effet de l’immunisation active, a l’aide d’un peptide correspondant a la deuxieme boucle extracellulaire des recepteurs adrenergiques (RA) β 1 , sur la reactivite de l’aorte isolee de rat Wistar. Methodes Des rats Wistar âges de neuf semaines ont ete activement immunises pendant trois mois avec un peptide correspondant a la deuxieme boucle extracellulaire des RA β 1 humains. Les immunoglobulines G (IgG) specifiques ont ete caracterisees par Elisa et quantifiees par la methode BCA. Leur fonctionnalite a ensuite ete testee dans des cardiomyocytes ventriculaires isoles (CVI). Des anneaux d’aorte de rats temoins ou immunises ont ete montes dans des cuves a organes isoles. Ensuite, des courbes de contraction a la phenylephrine (1 nM a 300 μM) ou de relaxation a l’acetylcholine (1 nM a 100 μM) et l’isoprenaline (1 nM a 30 μM) ont ete etablies. Resultats Dans les CVI, les IgG anti-RA β 1 (10 ou 25 μg/mL) induisent une augmentation du raccourcissement cellulaire dependante de la concentration. L’effet inotrope positif induit par l’isoprenaline (10 nM et 1 μM) est fortement reduit dans les CVI incubes en presence de 25 μg/mL d’IgG pendant trois heures. Dans l’aorte de rats immunises, la contraction a la phenylephrine et la relaxation a l’acetylcholine sont significativement alterees. En revanche, la relaxation induite par l’isoprenaline est conservee. Conclusions Cette etude confirme que les anticorps diriges contre la deuxieme boucle extracellulaire des RA β 1 induisent un effet inotrope positif dans les cardiomyocytes isoles de rat adulte. Elle montre aussi, pour la premiere fois, que les rats immunises presentent une alteration de la fonction endotheliale, mais une conservation de la relaxation adrenergique β.

Aims An extensive variety of prenatal insults are associated with an increased incidence of metabolic and cardiovascular disorders in adult life. We previously demonstrated that maternal global nutrient restriction during pregnancy leads to increased blood pressure and endothelial dysfunction in the adult offspring. This study aimed to assess whether prenatal exposure to nutritional insult has transgenerational effects in F 2 and F 3 offspring. Main methods For this, female Wistar rats were randomly divided into two groups on day 1 of pregnancy: a control group fed standard chow ad libitum and a restricted group fed 50% of the ad libitum intake throughout gestation. At delivery, all animals were fed a standard laboratory chow diet. At 11 weeks of age, one female and one male from each restricted litter were randomly selected and mated with rats from another restricted litters in order to generate the F 2 offspring. The same procedure produced F 3 generation. Similarly, the rats in the control group were bred for each generation. Key Findings Our findings show that the deleterious effects of maternal nutrient restriction to which the F 0 mothers were exposed may not be limited to the male first generation. In fact, we found that elevated blood pressure, an impaired vasodilatory response to acetylcholine and alterations in NO production were all transferred to the subsequent males from F 2 and F 3 generations. Significance Our data show that global nutrient restriction during pregnancy results in a specific phenotype that can be passed transgenerationally to a second and third generation.

Kinin B(1) and B(2) receptors play an essential role in inflammatory process and cardiovascular homeostasis. The present study investigated the vascular reactivity and nitric oxide (NO) generation in the isolated mesenteric arteriolar bed from B(1) (B(1)(-/-)) and B(2) receptor (B(2)(-/-)) knockout mice. Endothelial-dependent relaxation was significantly decreased in arterioles from both B(1)(-/-) and B(2)(-/-) in comparison to wild type (WT) mice, with no differences for endothelial-independent relaxating or vasoconstrictor agents. Plasmatic and vascular NO production were markedly reduced in both B(1)(-/-) and B(2)(-/-). In contrast, in the presence of l-arginine, Ca(2+) and co-factors for the enzyme, NO synthase activity was higher in homogenates of mesenteric vessels of B(1)(-/-) and B(2)(-/-). The present study demonstrated that targeted deletion of B(1) or B(2) receptor gene in mice induces important alterations in the vascular reactivity of resistance vessels and NO metabolism. The severe impairment in the endothelial-mediated vasodilation accompanied by decreased NO bioavailability, despite the augmented NOS activity, strongly indicates an exacerbation of NO inactivation in B(1)(-/-) and B(2)(-/-) vessels. The present data provide valuable information in order to clarify the relevance of kinin receptors in regulating vascular physiology and may point to new approaches regarding its correlation with endothelial dysfunction, oxidative stress and NO availability.

International audience; Major depression is an independent risk factor for the development of cardiovascular disease. This impact of depression on vascular function seems to be mediated by the endothelial dysfunction, defined as an impairment of endothelium-dependent vasorelaxation, which represents a reliable predictor of atherosclerosis and has been regularly found to be associated with depression. This study aimed at investigating aortic vascular reactivity in mice submitted to the unpredictable chronic mild stress (UCMS) procedure, a reliable model of depression. The results confirm the effectiveness of the UCMS procedure to induce neuroendocrine, physical and behavioral depression-like alterations as well as a significant decrease of acetylcholine-induced vasorelaxation without any effect on phenylephrine-induced vasoconstriction. In this study, we reveal an altered vascular reactivity in an animal model of depression, demonstrating an endothelial dysfunction reminiscent to the one found in depressed patients.

Although the development of the drug-eluting stent (DES) is a milestone in the field of interventional cardiovascular treatment, 20%-30% of patients suffer from restenosis within 3 months after surgery. This study explored the drug release frompaclitaxel+hirudin-eluting balloons in a healthy pig

Deposition of beta-amyloid along cerebral vessels is found in most patients suffering from Alzheimer's disease. The effects of cerebral amyloid angiopathy (CAA) on the function of cerebral blood vessels were analyzed applying cerebral blood volume (CBV)-based fMRI to transgenic arcA beta mice. In a cortical brain region of interest (ROI), displaying high CAA, arcA beta mice older than 16 months showed reduced response to the vasodilatory substance acetazolamide compared to age-matched wild-type animals, both with regard to rate (vascular reactivity) and extent of vasodilation (maximal vasodilation). In a subcortical ROI, displaying little CAA, no genotype-specific decrease was observed, but maximal vasodilation decreased with age in arcA beta and wild-types. These findings indicate that vascular beta-amyloid deposits reduce the capacity of cerebral blood vessels to dilate upon demand, supporting the hypothesis that vascular beta-amyloid contributes to hypoperfusion and neurological deficits observed in AD and CAA. High diagnostic accuracy of the combined readouts in detecting vascular dysfunction in arcA beta mice was found.

Although the excess of thyroid hormones has been found to be associated with many effects on the heart and vasculature, the adaptive changes of various conductive and resistance arteries from different vasculature are largely unknown. In this study, we compared changes in vascular reactivity between aortic and femoral arterial rings in hyperthyroidism rat model. Our results indicate that daily gastric feeding of euthyrox to rat with dosage of 100 microg group (H1) or 200 microg group (H2) for 25 days was sufficient to induce a thyrotoxicosis. The serum TT3 and TT4 levels, heart weight (HW), body weight (BW), HW/BW ratio and mean diameter of myocardiac cells of the rat were significantly greater (P0.05) in that two hyperthyroidism groups than in control group (E). It demonstrates that the gastric feeding of euthyrox may provide a reliable, cheaper and convenient method to induce hyperthyroid state with varying severity and duration. Our results also suggest that the contractile responses to phenylephrine (PE) and the relaxation responses to acetylcholine (Ach) or sodium nitroprusside (SNP) were reduced and enhanced, respectively, in vascular rings from H1 and H2 rats compared with E rats (P0.05). The above vasoconstriction and vasorelaxation responses to agonists at least in large, elastic and medium-sized muscular arteries, which might be important vascular changes accounting for the enhancement of ventriculoatrial coupling and the reduction in peripheral vascular resistance during hyperthyroidism.

Objectives: We investigated the relationship between coronary vascular reactivity and functional capacity as assessed from the Duke Activity Status Index (DASI) in a cohort of women evaluated for s...

Background The regulation of nutritive blood flow to skeletal muscles during exercise seems to make an important contribution to exercise capacity. In congestive heart failure (CHF) this regulation seems to be impaired, with attenuated peripheral vasodilatory capacity. The results regarding improvement of peripheral vasoreactivity after heart transplantation (HTx) are conflicting, and the contribution of impaired peripheral vasoreactivity to the observed reduced exercise capacity among heart transplant recipients (HTR) has not been well elucidated. We therefore assessed the reversibility of impaired vasoreactivity in forearm and calf after HTx with relationship to exercise capacity. Methods and Results The vasoreactivity of both forearm and calf was studied with venous occlusion plethysmography and related to exercise capacity in 64 patients with CHF and in 22 controls. Of these patients, 29 patients underwent HTx, and the same measurements were performed 10 days, 6 months and 1 year after HTx, and in a group of 15 HTR who had undergone HTx several years ago. Our main findings were (1) impaired resting blood flow in patients with CHF improved after HTx and even surpassed levels of controls; (2) peak forearm blood flow remained attenuated early after HTx, but normalized during the first year postoperatively; (3) both forearm and calf minimal resistance remained elevated after HTx; (4) vascular reactivity displays regional variations in forearm and calf both during CHF and after HTx; and (5) peripheral vascular reactivity relate to exercise performance in both patients with CHF and HTR, but the relationship seemed more pronounced in CHF. Conclusion With impaired vasoreactivity related to limited exercise capacity in CHF, improvement is evident after HTx, but both forearm and calf minimal resistance remains elevated. These findings suggest increased vasoconstrictor drive to both exercising and non-exercising muscles, possibly contributing to persistent physical limitation after HTx.

Transcranial Doppler ultrasonography (TCD) was introduced in 1982 by Aaslid and colleagues 5 as a non-invasive technique for monitoring blood flow velocity (FV) in the basal cerebral arteries. It is now increasingly being used in anaesthesia and intensive care for research as well as in clinical practice. The purpose of this review is to present: the basic concepts of TCD; the current status of the information obtained; its use of assessment of vascular reactivity; and applications in anaesthesia and intensive care.

Background The first response to perivascular injury is observed in the adventitial layer. The purpose of this study was to determine the time course of vascular reactivity alterations after collar injury in rats. We also analyzed the relation between adventitial layer injury and vascular responsiveness to vasoconstrictor agents. Methods Wistar rats had a silicone collar positioned around the carotid artery. The ipsilateral and contralateral arteries were morphologically analyzed 4, 7, 14 and 28 days after injury, and cumulative concentration–response curves to phenylephrine (Phe), angiotensin II (Ang II) and KCl were obtained for arteries isolated from collared and sham-operated groups. Results Inflammatory cells and fibroblasts were observed in the adventitial layer of collared arteries 4, 7, 14 and 28 days after injury. Intimal thickening was observed in collared arteries only 14 and 28 days after perivascular injury. A decrease in maximum effect values (Emax) for Phe, Ang II and KCl was observed in the collared artery when compared with the contralateral artery at all times after injury, whereas an increase in vascular responsiveness was observed in the contralateral artery 4 days after injury. Conclusions The impairment of the contractile response preceded the intimal thickening. The compromise of vascular reactivity coincided with the presence of inflammatory cells and angiogenesis in the adventitial layer. The enhancement of the efficacy and potency of Ang II and Phe in collared-contralateral arteries 4 days after collar placement may be related to a receptor-mediated compensatory mechanism stimulated by the collar injury.

It has been suggested that the combination of dietary Ca and Ca 2+ channel antagonists could have a synergic antihypertensive effect. In this study, 3-week-old male spontaneously hypertensive rats (SHR) were randomized into four groups of animals. Two of these groups were fed on a normal Ca diet (Ca 1%) and the other two groups were fed on a Ca-enriched diet (Ca 2.5%). One of the groups fed on each diet also received amlodipine (1 mg/kg/day) in their drinking water. Systolic and diastolic arterial blood pressure were measured weekly in the rats, from the 6th week of life until the 25th week of life, by the tail-cuff method, and we also calculated the corresponding pulse pressure values (systolic blood pressure−diastolic blood pressure). Determination of plasma Ca levels by colourimetric methods, and measurement in pithed rats of the pressor responses to the α-adrenoceptor agonists methoxamine and B-HT 920 (5-allyl-2-amino-5,6,7,8-tetrahydro-4 H -thiazolo-(4,5- d )-acepin-dihydrochloride, talixepole) were also performed using 16- and 23-week-old animals from the different groups. The Ca-enriched diet decreased systolic and diastolic blood pressure in SHR. Almodipine also decreased systolic and diastolic blood pressure in SHR, and this drug intensified the antihypertensive effect of the Ca 2.5% diet in the SHR between weeks 13 and 18. Nevertheless, in the 19- to 25-week-old SHR amlodipine antagonized the effect of dietary Ca on arterial blood pressure. A decrease in the pulse pressure was seen only in the 15- to 20-week-old SHR which had been simultaneously treated with dietary Ca and amlodipine. All the treatments used increased calcaemia, and the highest plasma Ca levels were obtained in the animals which had received the combined treatment with Ca and amlodipine. The responses to methoxamine and to B-HT 920 in the pithed 16-week-old SHR were similar in the four groups of animals. The responses to these agonists in the pithed 23-week-old SHR fed on the Ca-enriched diet were smaller than the corresponding responses in 23-week-old SHR of the untreated group. By contrast, the responses to these agonists were slightly higher in the pithed 23-week-old SHR which were treated with amlodipine than in the pithed 23-week-old SHR in the untreated group. Moreover, amlodipine partially reversed the effect of dietary Ca on α-vascular reactivity. According to our results, it would seem inadvisable to use dietary Ca with a Ca 2+ channel antagonist with the aim of controlling arterial blood pressure.

Objectives : This study was intended to evaluate the feasibility and applicability of assessing absolute myocardial blood flow (MBF) using O-15 water and PET 14 times for various doses of vasodilator challenges in miniature pigs. Methods and results : MBFs were quantitated following intravenous injection of O-15 water during various administration doses of adenosine (25–800 μg/kg/min) and A2A-selective CGS-21680 (0.5–20 μg/kg) in six miniature pigs. A low dose of adenosine increased MBF but reached to a maximum, and gradually decreased MBF with reduced heart rate (HR), reduced systolic blood pressure (SBP), and thus decreased RPP, together with prolonged PR interval. Reduction in HR, SBP and RPP were also observed with CGS-21680, but were significantly less, and the maximum MBF was greater with CGS-21680. These findings were consistent and reproducible among all the six subjects. Discussion and conclusion : The technique of assessing MBF with O-15 water and PET appeared to be reproducible and useful for quantitative evaluation of the vascular reactivity for various pharmacological/physiological stresses. The ability of accurately correcting for the partial volume effect, and recent advances of generating functional parametric images from the dynamic O-15 water alone, would be the most important factors in clinical usage of this methodology.

Au cours de la derniere decennie, plusieurs etudes ont montre que les anomalies vasculaires observees au cours du choc septique etaient liees a l'action de mediateurs inflammatoires sur l'endothelium vasculaire. Ce dernier joue un role central dans le controle du flux microcirculatoire. Dans de nombreux modeles experimentaux de choc septique, il a ete montre que l'activation de l'endothelium vasculaire, ainsi que son atteinte fonctionnelle et morphologique induite par le sepsis, etaient a l'origine de la survenue du syndrome de defaillance multiviscerale. Des preuves directes et indirectes d'atteinte des cellules endotheliales ont ete mises en evidence chez le patient. Cette mise au point presente les dernieres donnees de la litterature sur un sujet qui evolue rapidement.

The value of measuring projected area of transverse segment of hand nailfold capillary loops using computerized videophotometry was studied in 17 healthy individuals (10 women and 7 men) group A and 17 patients with diabetes type 2 (10 women and 7 men) group B with comparable ages (49.94+/-8.62 x 49.11+/-14.63 years old P=0.49). Videocapillaroscopy (VC) was performed under controlled temperature environment (24-26 degrees C). The test of post-occlusive reactive hyperemia was performed using a sphygmomanometer attached to the fourth left hand finger, 20 mmHg above maximum arterial pressure during 1 min. Images were captured each 2 s during 1 min. Time averages to reach the maximum post-ischemia area were determined as well as the area's increment percent in both groups. Both averages were compared by the Mann-Whitney test. There was no differences between area increments percent averages among controls and patients with diabetes (52.49+/-22.6 x 67.99+/-47.48% P=0.67), but the time to reach it during reperfusion was significantly increased among diabetics (5.52+/-2.96 x 18.58+/-8.08 s P0.0001).changes of capillary response to ischemia may be observed among patients with diabetes through bi-dimensional measures of projected area of capillary loops transverse segment in VC using a computerized system of image analysis. Patients with Diabetes mellitus do not have significantly different maximum area increments than controls, but spend more time to reach it during reperfusion.

To evaluate the effect of local anesthesia on the skin vasodilation induced by the iontophoresis of sodium nitroprusside and heating.Skin vascular reactivity, in response to iontophoresis of sodium nitroprusside (SNP), was evaluated at the forearm and foot in 13 neuropathic diabetic (DN) and 11 nonneuropathic diabetic (D) patients and 9 healthy, nondiabetic subjects who served as controls (C). The direct (DI) and nerve axon reflex-related (N-V) vasodilation were measured by using two single-point laser Doppler probes. The vasodilation in response to local warming was also assessed. A topical anesthetic was applied on the contralateral forearm and foot and all the measurements were repeated.Dermal anesthesia resulted in a reduction of the direct vasodilation to SNP at the forearm [C: 58.1 +/- 16, D: 60.6 +/- 11%, and DN: 48.3 +/- 37% (postanesthesia percentage of reduction; mean +/- SEM), P0.01] and at the foot in all three groups (D: 38.5 +/- 12%, P0.01; C: 27.2 +/- 14% and DN: 11.3 +/- 17.5%, P=NS). The N-V related vasodilation was very low before and did not change after local anesthesia. The postanesthesia hyperemic response to warming was significantly reduced at low temperatures but did not change at 44 degrees C.The sodium nitroprusside-related vasodilation is reduced after local anesthesia in a similar way in healthy subjects and diabetic patients with and without neuropathy. The response to heating is also reduced at low temperatures. This indicates a stabilizing effect of local anesthesia on the smooth muscle cell.

Twenty-five healthy and thirty-one preeclamptic pregnant women were assessed by means of transcranial Doppler sonography. Resting cerebral blood flow velocities in the middle cerebral arteries were measured followed by a repeat measurement 30 s after breath holding. Absolute blood flow velocities and per cent changes after breath holding procedure were compared between the groups. Absolute blood flow velocities were higher in preeclamptic pregnant women both at rest and after breath holding. The per cent increase in cerebral blood flow velocity after breath holding (cerebral vascular reactivity) was similar in the two groups. Our data suggest that cerebral vascular reactivity is preserved in pregnant women with preeclampsia.

Pathophysiological mechanisms involved in obesity include insulin resistance and endothelial dysfunction. It has been reported that endoplasmic reticulum stress (ERS) plays a key role in these mechanisms. Objective: To determine possible alterations in th

Background: Stress CT myocardial perfusion imaging (MPI) is an important functional adjunct to CT angiography (CTA). Stressor induced changes in epicardial diameter could provide index of vascular reactivity, but are not routinely assessed during MPI. Methods: Sequential CTA (120 kV, 350 mA) was

Evidence continues to accumulate on the importance of paracrine substances formed in the endothelium in regulation of the vascular system. Mechanisms that govern the balance between relaxing and contracting factors are important for understanding the regulation of blood vessel tone in health and disease. Chemical antagonism between superoxide anions and nitric oxide has been recognized as a potentially important modulator of vascular reactivity as well as being a source of peroxynitrite, a potent oxidant. In several models of vascular diseases, impairment of endothelium-dependent relaxations and promotion of endothelium-dependent contractions has been ascribed to increased production of superoxide anions. In pathologic conditions, increased production of superoxide anions may be responsible for an impairment of balance between relaxing and contracting factors favoring an increase in arterial tone. In this review the role of superoxide anions in modulation of endothelial mechanisms responsible for regulation of arterial tone will be discussed.