Effects of smoking cessation on endothelial function as assessed by flow-mediated total dilation.

BACKGROUND: In assessing the effects of smoking cessation on endothelial function, low-flow-mediated constriction (L-FMC) may provide complementary information to flow-mediated dilation (FMD). However, the value of flow-mediated total dilation (FMTD), an index that incorporates L-FMC into FMD, remains underreported. We aimed to evaluate the effect of smoking cessation on endothelial function, as assessed by FMD and FMTD, and clarify its associated clinical factors. METHODS: We enrolled 118 consecutive current smokers without previous coronary artery disease (72.9% were men; age: 59 ± 11 years) who underwent smoking cessation treatment. The clinical variables %FMD, %L-FMC, and %FMTD were examined before and 20 weeks after treatment initiation. A multivariate linear regression model was used to investigate the effects of smoking cessation on %FMD and %FMTD and the interaction between smoking cessation and baseline clinical variables. RESULTS: After 20 weeks, 85 smokers (69.4% were men; age: 59 ± 12 years) ceased smoking (abstainers), whereas 33 smokers (81.8% were men; age: 58 ± 11 years) did not (continued smokers). The estimated group differences (abstainers - continued smokers) in changes in the %FMD and %FMTD were 0.77% (95% confidence interval [CI], -0.22-1.77%; p = 0.129) and 1.17% (95% CI, 0.16-2.18%; p = 0.024), respectively. Smoking cessation-associated improvement in %FMTD was greater in women than in men (5.41% [95% CI, 3.15-7.67%] versus 0.24% [95% CI, -0.81-1.28%]; p-value for interaction, < 0.001). Additionally, a greater %FMTD improvement was observed in patients who smoked fewer cigarettes per day (p-value for interaction, 0.042) and those who had a smaller resting baseline lumen diameter (Dbase) (p-value for interaction, 0.023). CONCLUSIONS: Smoking cessation was associated with an improvement in %FMTD. Sex, cigarettes smoked per day, and Dbase significantly affected this improvement. The FMTD may help in risk stratification after smoking cessation.

Sex differences in CGRP-induced vasodilation of human middle meningeal arteries but not human coronary arteries: implications for migraine.

BACKGROUND: Migraine prevalence and levels of calcitonin gene-related peptide (CGRP), a peptide involved in migraine pathophysiology, differ between men and women, and appear to be affected by changes in sex hormones. The present study investigated the sex-specific responses to CGRP in human isolated arteries. METHODS: CGRP-induced relaxation of 62 (28 men and 34 women) human isolated middle meningeal arteries (HMMA) and 139 (69 men and 70 women) human isolated coronary arteries (HCA) was compared between men and women in groups <50 years and ≥50 years of age as a proxy for pre- and postmenopausal status in women, as well as matched-age groups for men. RESULTS: In HCA, no differences were observed between male and female tissue, or between the different age groups. However, in HMMA, the maximum response was significantly smaller and CGRP was less potent in females <50 compared with males <50 years of age. No differences were observed between the older age groups. CONCLUSIONS: Sex differences were observed for CGRP-induced relaxation of HMMA, but not HCA. These differences could arise from differential receptor expression in the vascular beds combined with the effect of sex hormones on CGRP and subsequent receptor desensitization.

Spontaneous vascular dysfunction in Dahl salt-sensitive male rats raised without a high-salt diet.

Dahl salt-sensitive (SS) rats fed a high-salt diet, but not low-salt, exhibit vascular dysfunction. Several substrains of SS rats exist that differ in their blood pressure phenotypes and salt sensitivity. The goal of this study was to investigate whether the John-Rapp-derived SS rat (SS/Jr), which exhibits spontaneous hypertension on a low-salt diet, presents with hallmarks of vascular dysfunction observed in another experimental model of hypertension independent of dietary salt, the spontaneously hypertensive rat (SHR). Endothelium-intact aortic rings and mesenteric resistance arteries were isolated from low-salt fed adult male SS/Jr rats and SHRs, or their respective controls, for isometric wire myography. Vessels were challenged with cumulative concentrations of various vasoactive substances, in the absence or presence of nitric oxide synthase or cyclooxygenase inhibitors. Despite showing some differences in their responses to various vasoactive substances, both SS/Jr rats and SHRs exhibited key features of vascular dysfunction, including endothelial dysfunction and hyperresponsiveness to vasocontractile agonists. In conclusion, this study provides evidence to support the utility of the SS/Jr rat strain maintained on a low-salt diet as a valid experimental model for vascular dysfunction, a key feature of human hypertension.

Influence of heart failure (HF) comorbidity in chronic obstructive pulmonary disease (COPD) and isolated forms of HF and COPD on cardiovascular function during hospitalization.

INTRODUCTION: Coexistence of chronic obstructive pulmonary disease(COPD) and heart failure(HF) is associated with systemic inflammation, myocardial injury, and arterial stiffening, impacting cardiovascular risk and prognosis in patients. Arterial stiffness, reduced nitric oxide synthesis, and altered cardiac autonomic control further link COPD and HF pathophysiology, emphasizing the need for comprehensive cardiovascular assessment. OBJECTIVE: To investigate a cardiovascular profile in patients hospitalized with exacerbation COPD(ECOPD) in coexistence with HF compared with isolated diseases. METHODS: A cross-sectional study including patients diagnosed with ECOPD and decompensated HF, approached between 24 and 48 h after hospital admission. Assessments included: endothelial function by brachial artery flow-mediated vasodilation(FMD); hemodynamic through analysis of pulse wave and arterial stiffness by carotid-femoral pulse wave velocity(cfPWV) and cardiac autonomic modulation(CAM) by heart rate variability(HRV). RESULTS: The mean FMD was 4.45 %, indicating endothelial dysfunction in all patients. Date is present in mean(confidence interval) sequency COPD(n = 12), COPD-HF(n = 21) and HF(n = 21). FMD: 5.47(3.96-6.91); 2.66(0.09-3.48); 4.60(2.30-6.43) p < 0.01. However, COPD-HF had worse FMD. Arterial stiffens (AIx: 29.0(19.0-42.6); 34.6(24.3-43.2); 14.5(8.0-24.0)p < 0.01; cfPWV: (6.5(5.4-7.2); 7.7(7.0-8.5); 6.0(5.0-6.5)); COPD-HF also showed greater activation of the sympathetic nervous system compared to patients with isolated diseases (PNS: 1.32(-2.53 to -0.62); -2.33(-2.60 to -2.12); -1.32(-1.42 to -1.01) p < 0.01; SNS: 3.50(1.40-8.55); 7.11(5.70-8.29); 2.32(1.78-5.01) p < 0.01). In addition, rMSSD, NN50, pNN50, and TINN also indicate worse CAM in the COPD-HF group compared to isolated diseases. CONCLUSION: During hospitalization, the worst impairment in vascular function and cardiac autonomic modulation were found in patients with COPD and HF comorbidity compared to the isolated diseases(HF or COPD).

Exploring the Therapeutic Potential of C-Type Natriuretic Peptide for Preeclampsia.

BACKGROUND: Preeclampsia is a serious condition of pregnancy, complicated by aberrant maternal vascular dysfunction. CNP (C-type natriuretic peptide) contributes to vascular homeostasis, acting through NPR-B (natriuretic peptide receptor-B) and NPR-C (natriuretic peptide receptor-C). CNP mitigates vascular dysfunction of arteries in nonpregnant cohorts; this study investigates whether CNP can dilate maternal arteries in ex vivo preeclampsia models. METHODS: Human omental arteries were dissected from fat biopsies collected during cesarean section. CNP, NPR-B, and NPR-C mRNA expression was assessed in arteries collected from pregnancies complicated by preeclampsia (n=6) and normotensive controls (n=11). Using wire myography, we investigated the effects of CNP on dilation of arteries from normotensive pregnancies. Arteries were preconstricted with either serum from patients with preeclampsia (n=6) or recombinant ET-1 (endothelin-1; vasoconstrictor elevated in preeclampsia; n=6) to model vasoconstriction associated with preeclampsia. Preconstricted arteries were treated with recombinant CNP (0.001-100 µmol/L) or vehicle and vascular relaxation assessed. In further studies, arteries were preincubated with NPR-B (5 µmol/L) and NPR-C (10 µmol/L) antagonists before serum-induced constriction (n=4-5) to explore mechanistic signaling. RESULTS: CNP, NPR-B, and NPR-C mRNAs were not differentially expressed in omental arteries from preeclamptic pregnancies. CNP potently stimulated maternal artery vasorelaxation in our model of preeclampsia (using preeclamptic serum). Its vasodilatory actions were driven through the activation of NPR-B predominantly; antagonism of this receptor alone dampened CNP vasorelaxation. Interestingly, CNP did not reduce ET-1-driven omental artery constriction. CONCLUSIONS: Collectively, these data suggest that enhancing CNP signaling through NPR-B offers a potential therapeutic strategy to reduce systemic vascular constriction in preeclampsia.

A comprehensive physics-based model for the brachial Artery's full flow mediated dilation (FMD) response observed during the FMD test.

In this study, a physics-based model is developed to describe the entire flow mediated dilation (FMD) response. A parameter quantifying the arterial wall's tendency to recover arises from the model, thereby providing a more elaborate description of the artery's physical state, in concert with other parameters characterizing mechanotransduction and structural aspects of the arterial wall. The arterial diameter's behavior throughout the full response is successfully reproduced by the model. Experimental FMD response data were obtained from healthy volunteers. The model's parameters are then adjusted to yield the closest match to the observed experimental response, hence delivering the parameter values pertaining to each subject. This study establishes a foundation based on which future potential clinical applications can be introduced, where endothelial function and general cardiovascular health are inexpensively and noninvasively quantified.

Coronary and Systemic Vasodilator Responsiveness of Patients Receiving Conventional Intermittent or Nocturnal Hemodialysis.

BACKGROUND: Nocturnal hemodialysis (nHD) restores the attenuated brachial artery vasodilator responsiveness of patients receiving conventional intermittent hemodialysis (iHD). Its impact on coronary vasodilatation is unknown. METHODS: We evaluated 25 patients on hemodialysis who fulfilled transplant criteria: 15 on iHD (4-hour sessions, 3 d/wk) and 10 on nHD (≈40 h/wk over 8-10-hour sessions) plus 6 control participants. Following diagnostic angiography, left anterior descending (LAD) coronary flow reserve and mean luminal diameter were quantified at baseline and during sequential intracoronary administration of adenosine (infusion and bolus), nitroglycerin (bolus), acetylcholine (infusion), acetylcholine coinfused with vitamin C, and, finally, sublingual nitroglycerin. RESULTS: Coronary flow reserve in those receiving nHD was augmented relative to iHD (3.28±0.26 versus 2.17±0.12 [mean±SEM]; P<0.03) but attenuated, relative to controls (4.80±0.63; P=0.011). Luminal dilatations induced by intracoronary adenosine and nitroglycerin were similar in nHD and controls but blunted in the iHD cohort (P<0.05 versus both). ACh elicited vasodilatation in controls but constriction in both dialysis groups (both P<0.05, versus control); vitamin C coinfusion had no effect. Sublingual nitroglycerin increased mid-left anterior descending diameter and reduced mean arterial pressure in controls (+15.2±2.68%; -16.00±1.60%) and in nHD recipients (+14.78±5.46%; -15.82±1.32%); iHD responses were markedly attenuated (+1.9±0.86%; -5.89±1.41%; P<0.05, all comparisons). CONCLUSIONS: Coronary and systemic vasodilator responsiveness to both adenosine and nitroglycerin is augmented in patients receiving nHD relative to those receiving iHD, whereas vasoconstrictor responsiveness to acetylcholine does not differ. By improving coronary conduit and microvascular function, nHD may reduce the cardiovascular risk of patients on dialysis.

VPAC1 and VPAC2 receptors mediate tactile hindpaw hypersensitivity and carotid artery dilatation induced by PACAP38 in a migraine relevant mouse model.

BACKGROUND: Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide pivotal in migraine pathophysiology and is considered a promising new migraine drug target. Although intravenous PACAP triggers migraine attacks and a recent phase II trial with a PACAP-inhibiting antibody showed efficacy in migraine prevention, targeting the PACAP receptor PAC1 alone has been unsuccessful. The present study investigated the role of three PACAP receptors (PAC1, VPAC1 and VPAC2) in inducing migraine-relevant hypersensitivity in mice. METHODS: Hindpaw hypersensitivity was induced by repeated PACAP38 injections. Tactile sensitivity responses were quantified using von Frey filaments in three knockout (KO) mouse strains, each lacking one of the PACAP-receptors (Ntotal = 160). Additionally, ex vivo wire myography was used to assess vasoactivity of the carotid artery, and gene expression of PACAP receptors was examined by qPCR. RESULTS: PACAP38 induced hypersensitivity in WT controls (p < 0.01) that was diminished in VPAC1 and VPAC2 KO mice (p < 0.05). In contrast, PAC1 KO mice showed similar responses to WT controls (p > 0.05). Myograph experiments supported these findings showing diminished vasoactivity in VPAC1 and VPAC2 KO mice. We found no upregulation of the non-modified PACAP receptors in KO mice. CONCLUSIONS: This study assessed all three PACAP receptors in a migraine mouse model and suggests a significant role of VPAC receptors in migraine pathophysiology. The lack of hypersensitivity reduction in PAC1 KO mice suggests the involvement of other PACAP receptors or compensatory mechanisms. The results indicate that targeting only individual PACAP receptors may not be an effective migraine treatment.

Stimulation of the calcium-sensing receptor induces relaxations through CGRP and NK1 receptor-mediated pathways in male rat mesenteric arteries.

Stimulation of the calcium-sensing receptor (CaSR) regulates vascular contractility, but cellular mechanisms involved remain unclear. This study investigated the role of perivascular sensory nerves in CaSR-induced relaxations of male rat mesenteric arteries. In fluorescence studies, colocalisation between synaptophysin, a synaptic vesicle marker, and the CaSR was present in the adventitial layer of arterial segments. Using wire myography, increasing external Ca2+ concentration ([Ca2+]o) from 1 to 10 mM induced vasorelaxations, previously shown to involve the CaSR, which were inhibited by pretreatment with capsaicin. [Ca2+]o-induced vasorelaxations were partially reduced by the calcitonin gene-related peptide (CGRP) receptor blockers, CGRP 8-37 and BIBN 4096, and the neurokinin 1 (NK1) receptor blocker L733,060. The inhibitory effect of CGRP 8-37 required a functional endothelium whereas the inhibitory action of L733,060 did not. Complete inhibition of [Ca2+]o-induced vasorelaxations occurred when CGRP 8-37 and L733,060 were applied together. [Ca2+]o-induced vasorelaxations in the presence of capsaicin were abolished by the ATP-dependent K+ channel (KATP) blocker PNU 37883, but unaffected by the endothelium nitric oxide synthase (eNOS) inhibitor L-NAME. We suggest that the CaSR on perivascular sensory nerves mediate relaxations in rat mesenteric arteries via endothelium-dependent and -independent mechanisms involving CGRP and NK1 receptor-activated NO production and KATP channels, respectively.

Inhibition of Th17 cell differentiation by aerobic exercise improves vasodilatation in diabetic mice.

BACKGROUND: Aortic endothelial diastolic dysfunction is an early complication of diabetes and the abnormal differentiation of Th17 cells is involved in the development of diabetes. However, the exact role of exercise on regulating the Th17 cells differentiation and the underlying molecular mechanisms remain to be elucidated in diabetic mice. METHODS: db/db and db/m+ mice were randomly divided into exercise and sedentary groups. Mice in exercise group were exercised daily, 6 days/week, for 6 weeks and mice in sedentary groups were placed on a nonmoving treadmill for 6 weeks. Vascular endothelial function was measured via wire myograph and the frequencies of Th17 from peripheral blood in mice were assessed via flow cytometry. RESULTS: Our data showed that exercise improved insulin resistance and aortic endothelial diastolic function in db/db mice. In addition, the proportion of Th17 cells and IL-17A level in peripheral blood of db/db mice were significantly increased, and exercise could promote Th17 cell differentiation and reduce IL-17A level. More importantly, STAT3 or ROR-γt inhibitors could promote Th17 cell differentiation in db/db mice, while exercise significantly down-regulated p-STAT3/ROR-γt signaling in db/db mice, suggesting that exercise regulated Th17 differentiation through STAT3/ROR-γt signaling. CONCLUSIONS: This study demonstrated that exercise improved vascular endothelial function in diabetic mice via reducing Th17 cell differentiation through p-STAT3/ROR-γt pathway, suggesting exercise may be an important non-pharmacological intervention strategy for the treatment of diabetes-related vascular complications.

Serotonin receptor-mediated vasorelaxation occurs primarily through 5-HT4 activation in bovine lateral saphenous vein.

To better understand mechanisms of serotonin- (5-HT) mediated vasorelaxation, isolated lateral saphenous veins from cattle were assessed for vasoactivity using myography in response to increasing concentrations of 5-HT or selective 5-HT receptor agonists. Vessels were pre-contracted with 1 × 10-4 M phenylephrine and exposed to increasing concentrations of 5-HT or 5-HT receptor agonists that were selective for 5-HT1B, 5-HT2B, 5-HT4, and 5-HT7. Vasoactive response data were normalized as a percentage of the maximum contractile response induced by the phenylephrine pre-contraction. At 1 × 10-7 M 5-HT, a relaxation was observed with an 88.7% decrease (p < 0.01) from the phenylephrine maximum. At 1 × 10-4 M 5-HT, a contraction was observed with a 165% increase (p < 0.01) from the phenylephrine maximum. Increasing concentrations of agonists selective for 5-HT2B, 5-HT4, or 5-HT7 resulted in a 27%, 92%, or 44% (p < 0.01) decrease from the phenylephrine maximum, respectively. Of these 5-HT receptor agonists, the selective 5-HT4 receptor agonist resulted in the greatest potency (-log EC50) value (6.30) compared with 5-HT2B and 5-HT7 receptor agonists (4.21 and 4.66, respectively). To confirm the involvement of 5-HT4 in 5-HT-mediated vasorelaxation, blood vessels were exposed to either DMSO (solvent control) or a selective 5-HT4 antagonist (1 × 10-5 M) for 5-min prior to the phenylephrine pre-contraction and 5-HT additions. Antagonism of the 5-HT4 receptor attenuated the vasorelaxation caused by 5-HT. Approximately 94% of the vasorelaxation occurring in response to 5-HT could be accounted for through 5-HT4, providing strong evidence that 5-HT-mediated vasorelaxation occurs through 5-HT4 activation in bovine peripheral vasculature.

Ion Channels Remodeling in the Regulation of Vascular Hyporesponsiveness During Shock.

Shock is characterized with vascular hyporesponsiveness to vasoconstrictors, thereby to cause refractory hypotension, insufficient tissue perfusion, and multiple organ dysfunction. The vascular hyporeactivity persisted even though norepinephrine and fluid resuscitation were administrated, it is of critical importance to find new potential target. Ion channels are crucial in the regulation of cell membrane potential and affect vasoconstriction and vasodilation. It has been demonstrated that many types of ion channels including K+ channels, Ca2+ permeable channels, and Na+ channels exist in vascular smooth muscle cells and endothelial cells, contributing to the regulation of vascular homeostasis and vasomotor function. An increasing number of studies suggested that the structural and functional alterations of ion channels located in arteries contribute to vascular hyporesponsiveness during shock, but the underlying mechanisms remained to be fully clarified. Therefore, the expression and functional changes in ion channels in arteries associated with shock are reviewed, to pave the way for further exploring the potential of ion channel-targeted compounds in treating refractory hypotension in shock.

Endothelial Function Correlates With Pulmonary Pressures in Subjects With Clinically Suspected Pulmonary Hypertension.

Impaired pulmonary circulation hemodynamics are characteristic of pulmonary hypertension (PH). We therefore sought to evaluate possible correlations between endothelial function noninvasively assessed by brachial artery flow-mediated dilation (FMD) and hemodynamic parameters at right-sided cardiac catheterization in patients with clinically suspected PH. Consecutive outpatients with suspected PH were enrolled in the study. In all patients, endothelial function was assessed by FMD and hemodynamic parameters (pulmonary artery pressure [PAP]); pulmonary vascular resistances [PVR]) were derived by right-sided cardiac catheterization. For this study, 95 consecutive patients with suspected PH were enrolled (mean age 63 ± 13 years, 58% male) and included in the analysis. FMD values were significantly correlated with systolic (s)PAP levels (r = -0.29, p = 0.016); correlation with PVR was of borderline significance (r = -0.21, p = 0.78). After multivariable regression analysis including age, gender, tricuspid annular plane systolic excursion and peak tricuspid regurgitation velocity (peak TRV), and FMD, the latter remained significantly correlated with systolic pulmonary artery pressure (sPAP) values (B = -47, p = 0.02). After classifying patients according to median levels of peak TRV and FMD into 3 groups (neither, either, or both impaired), progressively increased levels of sPAP, mean PAP, and PVR were found (p for trend <0.001 in all cases). FMD values were inversely related to sPAP levels in a small population of patients with clinically suspected PH. In combination with peak TRV levels, FMD values noninvasively assessed were predictive of increased sPAP, mean PAP, and PVR.

Arterial function in response to a 50 km ultramarathon in recreational athletes.

This study was performed to determine whether prolonged endurance running results in acute endothelial dysfunction and wave-reflection, as endothelial dysfunction and arterial stiffness are cardiovascular risk factors. Vascular function (conduit artery/macrovascular and resistance artery/microvascular) was assessed in 11 experienced runners (8 males, 3 females) before, during and after a 50 km ultramarathon. Blood pressure (BP), heart rate (HR), wave reflection, augmentation index (AIx) and AIx corrected for HR (AIx75) were taken at all time points-Baseline (BL), following 10, 20, 30 and 40 km, 1 h post-completion (1HP) and 24 h post-completion (24HP). Flow-mediated dilatation (FMD) and inflammatory biomarkers were examined at BL, 1HP and 24HP. Reactive hyperaemia area under the curve (AUC) and shear rate AUC to peak dilatation were lower (∼75%) at 1HP compared with BL (P < 0.001 for both) and reactive hyperaemia was higher at 24HP (∼27%) compared with BL (P = 0.018). Compared to BL, both mean central systolic BP and mean central diastolic BP were 7% and 10% higher, respectively, following 10 km and 6% and 9% higher, respectively, following 20 km, and then decreased by 5% and 8%, respectively, at 24HP (P < 0.05 for all). AIx (%) decreased following 20 km and following 40 km compared with BL (P < 0.05 for both) but increased following 40 km when corrected for HR (AIx75) compared with BL (P = 0.02). Forward wave amplitude significantly increased at 10 km (15%) compared with BL (P = 0.049), whereas backward wave reflection and reflected magnitude were similar at all time points. FMD and baseline diameter remained similar. These data indicate preservation of macrovascular (endothelial) function, but not microvascular function resulting from the 50 km ultramarathon.

Nadir blood pressure responses to longer consecutive cardiac cycle sequences absent of sympathetic bursts are associated with popliteal endothelial-dependent dilation.

PURPOSE: The nadir pressure responses to cardiac cycles absent of muscle sympathetic nerve activity (MSNA) bursts (or non-bursts) are typically reported in studies quantifying sympathetic transduction, but the information gained by studying non-bursts is unclear. We tested the hypothesis that longer sequences of non-bursts (≥8 cardiac cycles) would be associated with a greater nadir diastolic blood pressure (DBP) and that better popliteal artery function would be associated with an augmented reduction in DBP. METHODS: Resting beat-by-beat DBP (via finger photoplethysmography) and common peroneal nerve MSNA (via microneurography) were recorded in 39 healthy, adults (age 23.4 ± 5.3 years; 19 females). For each cardiac cycle absent of MSNA bursts, the mean nadir DBP (ΔDBP) during the 12 cardiac cycles following were determined, and separate analyses were conducted for ≥8 or < 8 cardiac cycle sequences. Popliteal artery endothelial-dependent (via flow-mediated dilation; FMD) and endothelial-independent vasodilation (via nitroglycerin-mediated dilation; NMD) were determined. RESULTS: The nadir DBP responses to sequences ≥8 cardiac cycles were larger (-1.40 ± 1.27 mmHg) than sequences <8 (-0.38 ± 0.46 mmHg; p < 0.001). In adjusting for sex and burst frequency (14 ± 8 bursts/min), larger absolute or relative FMD (p < 0.01), but not NMD (p > 0.53) was associated with an augmented nadir DBP. This overall DBP-FMD relationship was similar in sequences ≥8 (p = 0.04-0.05), but not <8 (p > 0.72). CONCLUSION: The DBP responses to non-bursts, particularly longer sequences, were inversely associated with popliteal endothelial function, but not vascular smooth muscle sensitivity. This study provides insight into the information gained by quantifying the DBP responses to cardiac cycles absent of MSNA.

The role of pannexin/purinergic signaling in intervascular communication from capillaries during skeletal muscle contraction in male Golden hamsters.

We sought to determine the physiological relevance of pannexin/purinergic-dependent signaling in mediating conducted vasodilation elicited by capillary stimulation through skeletal muscle contraction. Using hamster cremaster muscle and intravital microscopy we stimulated capillaries through local muscle contraction while observing the associated upstream arteriole. Capillaries were stimulated with muscle contraction at low and high contraction (6 and 60CPM) and stimulus frequencies (4 and 40 Hz) in the absence and presence of pannexin blocker mefloquine (MEF; 10-5 M), purinergic receptor antagonist suramin (SUR 10-5 M) and gap-junction uncoupler halothane (HALO, 0.07%) applied between the capillary stimulation site and the upstream arteriolar observation site. Conducted vasodilations elicited at 6CPM were inhibited by HALO while vasodilations at 60CPM were inhibited by MEF and SUR. The conducted response elicited at 4 Hz was inhibited by MEF while the vasodilation at 40 Hz was unaffected by any blocker. Therefore, upstream vasodilations resulting from capillary stimulation via muscle contraction are dependent upon a pannexin/purinergic-dependent pathway that appears to be stimulation parameter-dependent. Our data highlight a physiological importance of the pannexin/purinergic pathway in facilitating communication between capillaries and upstream arteriolar microvasculature and, consequently, indicating that this pathway may play a crucial role in regulating blood flow in response to skeletal muscle contraction.

Similar endothelium-dependent vascular responses to intermittent hypoxia in young and older adults.

Aging is associated with vascular endothelial dysfunction observed through a progressive loss of flow-mediated dilation caused partly by a decreased nitric oxide bioavailability. Intermittent hypoxia, consisting of alternating short bouts of breathing hypoxic and normoxic air, was reported to either maintain or improve vascular function in young adults. The aim of this study was to determine the impact of age on the vascular response to intermittent hypoxia. Twelve young adults and 11 older adults visited the laboratory on two occasions. Plasma nitrate concentrations and brachial artery flow-mediated dilation were assessed before and after exposure to either intermittent hypoxia or a sham protocol. Intermittent hypoxia consisted of eight 4-min hypoxic cycles at a targeted oxygen saturation of 80% interspersed with breathing room air to resaturation, and the sham protocol consisted of eight 4-min normoxic cycles interspersed with breathing room air. Vascular responses were assessed during intermittent hypoxia and the sham protocol. Intermittent hypoxia elicited a brachial artery vasodilation but did not change brachial artery shear rate in both young and older adults. Plasma nitrate concentrations were not significantly affected by intermittent hypoxia compared with the sham protocol in both groups. Brachial artery flow-mediated dilation was not acutely affected by intermittent hypoxia or the sham protocol in either young or older adults. In conclusion, the brachial artery vasodilatory response to intermittent hypoxia was not influenced by age. Intermittent hypoxia increased brachial artery diameter but did not acutely affect endothelium-dependent vasodilation in young or older adults.NEW & NOTEWORTHY The objective of this study was to determine the impact of age on the vascular response to intermittent hypoxia. Eight 4-min bouts of hypoxia at a targeted oxygen saturation of 80% induced a brachial artery vasodilation in both young and older adults, indicating that age does not influence the vasodilatory response to intermittent hypoxia. Intermittent hypoxia did not acutely affect brachial artery flow-mediated dilation in young or older adults.

Effect of 60-Min Single Bout of Resistance Exercise, Reformer Pilates, on Vascular Function Parameters in Older Adults: A Randomized Crossover Study.

INTRODUCTION: Aging leads to vascular endothelial dysfunction and muscle impairment. While resistance exercise improves muscular function, its acute effects on vascular function vary in the literature, with some studies reporting detrimental effects. These findings indicate the need for exercises that optimize muscle function without compromising vascular function. Reformer Pilates (RP) is a low-impact exercise involving an adjustable sliding platform. However, the acute effects of RP on vascular function among older adults remain unknown. Therefore, this study aimed to investigate the acute effects of RP on vascular function in older adults. METHODS: Overall, 17 participants (age: 65 ± 2.76 years, body mass index: 23.42 ± 3.68 kg/m2) were examined and assigned to control and RP conditions under a randomized crossover design. The RP condition involved a 3.5-5 omnibus perceived exertion scale with 19 exercise postures for 60 min. Brachial artery flow-mediated dilation (FMD), brachial-ankle pulse wave velocity (baPWV), and blood pressure were measured at baseline and 0, 10, 30, and 60 min after exercise. RESULTS: RP significantly improved FMD at all time points compared with that at baseline (p < 0.05). baPWV increased at 0 min post-RP but returned to baseline levels at other time points. Additionally, RP showed improved FMD at 0, 10, and 30 min compared with that in the control condition (p < 0.05). However, no significant differences were observed in blood pressure or mean arterial pressure in either condition. CONCLUSION: RP enhanced FMD and regulated blood pressure for approximately 60 min post-exercise, suggesting its suitability for older adults to enhance vascular function and control blood pressure during exercise. Nonetheless, longitudinal resistance training intervention studies are needed to validate these findings.

New Research Could Help Explain Anger's Link to Heart Attacks and Strokes.

This Medical News article discusses a randomized clinical trial that investigated the effects of negative emotions on blood vessel dilation.

Effect of Incorporating 1 Avocado per Day Versus Habitual Diet on Vascular Function in Adults With Abdominal Obesity: An Ancillary Study of HAT, a Randomized Controlled Trial.

BACKGROUND: Abdominal obesity is associated with endothelial dysfunction and poorer vascular health. Avocado consumption improves postprandial endothelial function; however, the longer-term effects remain unclear. It was hypothesized that the daily addition of 1 avocado to a habitual diet for 6 months would improve flow-mediated dilation (FMD) and carotid-femoral pulse wave velocity in individuals with abdominal obesity (waist circumference ≥35 in for women, ≥40 in for men), compared with a habitual diet low in avocados. METHODS AND RESULTS: HAT (Habitual Diet and Avocado Trial) was a multicenter, randomized, controlled, parallel-arm study that investigated the health effects of adding 1 avocado per day to a habitual diet in individuals with abdominal obesity. At the Pennsylvania State University, University Park study center (n=134; age, 50 ± 13 years; women, 78%; body mass index, 32.6 ± 4.8 kg/m2), markers of vascular function were measured, including endothelial function, assessed via brachial artery flow-mediated dilation, and arterial stiffness, assessed via carotid-femoral pulse wave velocity. Between-group differences in 6-month change in flow-mediated dilation and carotid-femoral pulse wave velocity were assessed using independent t tests. Prespecified subgroup analyses were conducted using linear regression. No significant between-group differences in flow-mediated dilation (mean difference=-0.62% [95% CI, -1.70 to 0.46]) or carotid-femoral pulse wave velocity (0.25 m/s [95% CI, -0.13 to 0.63]) were observed. Results of the subgroup analyses were consistent with the primary analyses. CONCLUSIONS: Longer-term consumption of 1 avocado per day as part of a habitual diet did not improve measures of vascular function compared with a habitual diet low in avocados in individuals with abdominal obesity. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03528031.