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Acute aerobic exercise produces post-exercise hypotension (PEH). Chinese populations have lower prevalence of cardiovascular disease compared to Caucasians. PEH may be associated cardiovascular disease through its influence on hypertension. The purpose of this study was to compare PEH between Caucasian and Chinese subjects following acute aerobic exercise. 62 (30 Caucasian and 32 Chinese, 50% male) subjects underwent measurement of peripheral and central hemodynamics as well as arterial and cardiac evaluations, 30 min and 60 min after 45 min of treadmill exercise. Caucasians exhibited significantly higher baseline BP than the Chinese. While the reduction in brachial artery systolic BP was greater in Caucasian than in the Chinese, there was no difference in changes in carotid systolic BP between the groups. The increase in cardiac output and heart rate was greater in the Chinese than Caucasians, but total peripheral resistance and leg pulse wave velocity decreased by a similar magnitude in the Chinese and Caucasian subjects. We conclude that acute aerobic exercise produces a greater magnitude of PEH in peripheral systolic BP in Caucasian compared to Chinese subjects. The different magnitude in PEH was caused by the greater increase in cardiac output mediated by heart rate, with no change in stroke volume. It is possible that initial BP differences between races influenced the findings. [ABSTRACT FROM AUTHOR]

Background: Arterial stiffness and large artery function are independent risk factors for cardiovascular disease.(1) Individuals with Down Syndrome (DS) have autonomic dysfunction and known to have lower incidence of cardiovascular disease.(2) Limited literatures showed no difference in arterial stiffness in DS compared to a healthy, non-DS population using a longitudinal view of the carotid artery.(3,4) However, it is unknown if individuals with DS exhibit different circumferential strain compared to individuals without DS at rest or during a sympathoexcitation stimulus. Purpose: To examine the differences in the carotid artery strain and its responsiveness to sympathoexcitation by hypovolemic lower body negative pressure (LBNP) in individuals with and without DS. Methods: Twenty four volunteers (DS=11, 23 yrs Control=13, 23 yrs) participated in this study. Circumferential strain was measured by ultrasonography B-mode and radial strain from the longitudinal view was calculated using echo tracking analysis at rest, during and after sympathoexcitatory stimulation by LBNP. Changes in hemodynamics (HR, BP) were recorded continuously. Results: Compared with controls, individuals with DS have significantly higher strain values at all stages (p < 0.05) with no group interaction with hypovolemic sympathoexcitation stimulation. However, there were no differences in β-Stiffness or EP, suggesting that the differences in strain were due to differences in blood pressure. Conclusions: Our results demonstrate significantly higher strain value, which indicates greater arterial movement in individuals with DS. However, these differences were likely due to higher BP in persons with DS.

Peripheral microvascular dysfunction has been documented in patients with heart failure with preserved ejection fraction (HFpEF), which may be related to elevated levels of inflammation and oxidative stress. Unfortunately, few strategies have been identified to effectively ameliorate this disease-related derangement. Thus, using a parallel, double-blind, placebo-controlled design, this study evaluated the efficacy of 30-day atorvastatin administration (10 mg daily) on lower limb microvascular reactivity, functional capacity, and biomarkers of inflammation and oxidative stress in patients with HFpEF (statin, n = 8, 76 ± 6 yr; placebo, n = 8, 68 ± 9 yr). The passive limb movement (PLM)-induced hyperemic response and 6-min walk test (6MWT) distance were evaluated to assess ambulatory muscle microvascular function and functional capacity, respectively. Circulating biomarkers were also measured to assess the contribution of changes in inflammation and redox balance to these outcomes. The total hyperemic response to PLM, assessed as leg blood flow area under the curve (LBF AUC ), increased following the statin intervention (pre, 60 ± 68 mL; post, 164 ± 90 mL; P < 0.01), whereas these variables were unchanged in the placebo group ( P = 0.99). There were no significant differences in 6MWT distance following statin or placebo intervention. Malondialdehyde (MDA), a marker of lipid peroxidation, was significantly reduced following the statin intervention (pre, 0.68 ± 0.10; post, 0.51 ± 0.11; P < 0.01) while other circulating biomarkers were unchanged. Together, these data provide new evidence for the efficacy of low-dose statin administration to improve locomotor muscle microvascular reactivity in patients with HFpEF, which may be due, in part, to a diminution in oxidative stress. NEW & NOTEWORTHY This was the first study to investigate the impact of statin administration on locomotor muscle microvascular function in patients with HFpEF. In support of our hypothesis, the total hyperemic response to PLM, assessed as leg blood flow area under the curve, increased, and malondialdehyde, a marker of oxidative damage, was reduced following the statin intervention. Together, these data provide new evidence for the efficacy of statin administration to improve locomotor muscle microvascular reactivity in patients with HFpEF, which may be due, in part, to reduced oxidative stress.

Nighttime blood pressure (BP) and BP dipping (daytime-nighttime BP) are prognostic for cardiovascular disease. When compared with other racial/ethnic groups, Black Americans exhibit elevated nighttime BP and attenuated BP dipping. Neighborhood deprivation may contribute to disparities in cardiovascular health, but its effects on resting and ambulatory BP patterns in young adults are unclear. Therefore, we examined associations between neighborhood deprivation with resting and nighttime BP and BP dipping in young Black and White adults. We recruited 19 Black and 28 White participants (23 males/24 females, 21 ± 1 yr, body mass index: 26 ± 4 kg/m 2 ) for 24-h ambulatory BP monitoring. We assessed resting BP, nighttime BP, and BP dipping (absolute dip and nighttime:daytime BP ratio). We used the area deprivation index (ADI) to assess average neighborhood deprivation during early and mid-childhood and adolescence. When compared with White participants, Black participants exhibited higher resting systolic and diastolic BP ( Ps ≤ 0.029), nighttime systolic BP (114 ± 9 vs. 108 ± 9 mmHg, P = 0.049), diastolic BP (63 ± 8 vs. 57 ± 7 mmHg, P = 0.010), and attenuated absolute systolic BP dipping (12 ± 5 vs. 9 ± 7 mmHg, P = 0.050). Black participants experienced greater average ADI scores compared with White participants [110 (10) vs. 97 (22), P = 0.002], and select ADI scores correlated with resting BP and some ambulatory BP measures. Within each race, select ADI scores correlated with some BP measures for Black participants, but there were no ADI and BP correlations for White participants. In conclusion, our findings suggest that neighborhood deprivation may contribute to higher resting BP and impaired ambulatory BP patterns in young adults warranting further investigation in larger cohorts. NEW & NOTEWORTHY We demonstrate that young Black adults exhibit higher resting blood pressure, nighttime blood pressure, and attenuated systolic blood pressure dipping compared with young White adults. Black adults were exposed to greater neighborhood deprivation, which demonstrated some associations with resting and ambulatory blood pressure. Our findings add to a growing body of literature indicating that neighborhood deprivation may contribute to increased blood pressure.

Heart failure with preserved ejection fraction (HFpEF) is characterized by impaired vascular endothelial function that may be improved by hydroxy-methylglutaryl-CoA (HMG-CoA) reductase enzyme inhibition. Thus, using a parallel, double-blind, placebo-controlled design, this study evaluated the efficacy of 30-day atorvastatin administration (10 mg daily) on peripheral vascular function and biomarkers of inflammation and oxidative stress in 16 patients with HFpEF [Statin: n = 8, 74 ± 6 yr, ejection fraction (EF) 52-73%; Placebo: n = 8, 67 ± 9 yr, EF 56-72%]. Flow-mediated dilation (FMD) and sustained-stimulus FMD (SS-FMD) during handgrip (HG) exercise, reactive hyperemia (RH), and blood flow during HG exercise were evaluated to assess conduit vessel function, microvascular function, and exercising muscle blood flow, respectively. FMD improved following statin administration (pre, 3.33 ± 2.13%; post, 5.23 ± 1.35%; P < 0.01), but was unchanged in the placebo group. Likewise, SS-FMD, quantified using the slope of changes in brachial artery diameter in response to increases in shear rate, improved following statin administration (pre: 5.31 e -5  ± 3.85 e -5  mm/s -1 ; post: 8.54 e -5  ± 4.98 e -5  mm/s -1 ; P = 0.03), with no change in the placebo group. Reactive hyperemia and exercise hyperemia responses were unchanged in both statin and placebo groups. Statin administration decreased markers of lipid peroxidation (malondialdehyde, MDA) (pre, 0.652 ± 0.095; post, 0.501 ± 0.094; P = 0.04), whereas other inflammatory and oxidative stress biomarkers were unchanged. Together, these data provide new evidence for the efficacy of low-dose statin administration to improve brachial artery endothelium-dependent vasodilation, but not microvascular function or exercising limb blood flow, in patients with HFpEF, which may be due in part to reductions in oxidative stress. NEW & NOTEWORTHY This is the first study to investigate the impact of statin administration on vascular function and exercise hyperemia in patients with heart failure with preserved ejection fraction (HFpEF). In support of our hypothesis, both conventional flow-mediated dilation (FMD) testing and brachial artery vasodilation in response to sustained elevations in shear rate during handgrip exercise increased significantly in patients with HFpEF following statin administration, beneficial effects that were accompanied by a decrease in biomarkers of oxidative damage. However, contrary to our hypothesis, reactive hyperemia and exercise hyperemia were unchanged in patients with HFpEF following statin therapy. These data provide new evidence for the efficacy of low-dose statin administration to improve brachial artery endothelium-dependent vasodilation, but not microvascular reactivity or exercising muscle blood flow in patients with HFpEF, which may be due in part to reductions in oxidative stress.

Heart failure with preserved ejection fraction (HFpEF) accounts for over 50% of all heart failure cases nationwide and continues to rise in its prevalence. The complex, multi-organ involvement of the HFpEF clinical syndrome requires clinicians and investigators to adopt an integrative approach that considers the contribution of both cardiac and non-cardiac function to HFpEF pathophysiology. Thus, this symposium review outlines the key points from presentations covering the contributions of disease-related changes in cardiac function, arterial stiffness, peripheral vascular function, and oxygen delivery and utilization to exercise tolerance in patients with HFpEF. While many aspects of HFpEF pathophysiology remain poorly understood, there is accumulating evidence for a decline in vascular health in this patient group that may be remediable through pharmacological and lifestyle interventions and could improve outcomes and clinical status in this ever-growing patient population., (© 2023 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Heart failure with preserved ejection fraction (HFpEF) is associated with autonomic dysregulation, which may be related to baroreflex dysfunction. Thus, we tested the hypothesis that cardiac and peripheral vascular responses to baroreflex activation via lower-body negative pressure (LBNP; -10, -20, -30, -40 mmHg) would be diminished in patients with HFpEF ( n = 10, 71 ± 7 yr) compared with healthy controls (CON, n = 9, 69 ± 5 yr). Changes in heart rate (HR), mean arterial pressure (MAP, Finapres), forearm blood flow (FBF, ultrasound Doppler), and thoracic impedance (Z) were determined. Mild levels of LBNP (-10 and -20 mmHg) were used to specifically assess the cardiopulmonary baroreflex, whereas responses across the greater levels of LBNP represented an integrated baroreflex response. LBNP significantly increased in HR in CON subjects at -30 and -40 mmHg (+3 ± 3 and +6 ± 5 beats/min, P < 0.01), but was unchanged in patients with HFpEF across all LBNP levels. LBNP provoked progressive peripheral vasoconstriction, as quantified by changes in forearm vascular conductance (FVC), in both groups. However, a marked (40%-60%) attenuation in FVC responses was observed in patients with HFpEF (-6 ± 8, -15 ± 6, -16 ± 5, and -19 ± 7 mL/min/mmHg at -10, -20, -30, and -40 mmHg, respectively) compared with controls (-15 ± 10, -22 ± 6, -25 ± 10, and -28 ± 10 mL/min/mmHg, P < 0.01). MAP was unchanged in both groups. Together, these data provide new evidence for impairments in cardiopulmonary baroreflex function and diminished cardiovascular responsiveness during hypovolemia in patients with HFpEF, which may be an important aspect of the disease-related changes in autonomic cardiovascular control in this patient group. NEW & NOTEWORTHY Data from the current study demonstrate diminished cardiovascular responsiveness during hypovolemia induced by incremental lower-body negative pressure in patients with heart failure with preserved ejection fraction (HFpEF). These diminished responses imply impaired cardiopulmonary baroreflex function and altered autonomic cardiovascular regulation which may represent an important aspect of HFpEF pathophysiology.

Patients with heart failure with reduced (HFrEF) and preserved ejection fraction (HFpEF) exhibit severe exercise intolerance that may be due, in part, to inappropriate cardiovascular and hemodynamic adjustments to exercise. Several neural mechanisms and locally released vasoactive substances work in concert through complex interactions to ensure proper adjustments to meet the metabolic demands of the contracting skeletal muscle. Specifically, accumulating evidence suggests that disease-related alterations in neural mechanisms (e.g., central command, exercise pressor reflex, arterial baroreflex, and cardiopulmonary baroreflex) contribute to heightened sympathetic activation and impaired ability to attenuate sympathetic vasoconstrictor responsiveness that may contribute to reduced skeletal muscle blood flow and severe exercise intolerance in patients with HFrEF. In contrast, little is known regarding these important aspects of physiology in patients with HFpEF, though emerging data reveal heightened sympathetic activation and attenuated skeletal muscle blood flow during exercise in this patient population that may be attributable to dysregulated neural control of the circulation. The overall goal of this review is to provide a brief overview of the current understanding of disease-related alterations in the integrative neural cardiovascular responses to exercise in both HFrEF and HFpEF phenotypes, with a focus on sympathetic nervous system regulation during exercise.

Exercising muscle blood flow is reduced in patients with heart failure with a preserved ejection fraction (HFpEF), which may be related to disease-related changes in the ability to overcome sympathetic nervous system (SNS)-mediated vasoconstriction during exercise, (i.e., "functional sympatholysis"). Thus, in 12 patients with HFpEF (69 ± 7 yr) and 11 healthy controls (Con, 69 ± 4 yr), we examined forearm blood flow (FBF), mean arterial pressure (MAP), and forearm vascular conductance (FVC) during rhythmic handgrip exercise (HG) at 30% of maximum voluntary contraction with or without lower-body negative pressure (LBNP, -20 mmHg) to increase SNS activity and elicit peripheral vasoconstriction. SNS-mediated vasoconstrictor responses were determined as LBNP-induced changes (%Δ) in FVC, and the "magnitude of sympatholysis" was calculated as the difference between responses at rest and during exercise. At rest, the LBNP-induced change in FVC was significantly lesser in HFpEF compared with Con (HFpEF: -9.5 ± 5.5 vs. Con: -21.0 ± 8.0%; P < 0.01). During exercise, LBNP-induced %ΔFVC was significantly attenuated in Con compared with rest (HG: -5.8 ± 6.0%; P < 0.05) but not in HFpEF (HG: -9.9 ± 2.5%; P = 0.88). Thus, the magnitude of sympatholysis was lesser in HFpEF compared with Con (HFpEF: 0.4 ± 4.7 vs. Con: -15.2 ± 11.8%; P < 0.01). These data demonstrate a diminished ability to attenuate SNS-mediated vasoconstriction in HFpEF and provide new evidence suggesting impaired functional sympatholysis in this patient group. NEW & NOTEWORTHY Data from the current study suggest that functional sympatholysis, or the ability to adequately attenuate sympathetic nervous system (SNS)-mediated vasoconstriction during exercise, is impaired in patients with heart failure with preserved ejection fraction (HFpEF). These observations extend the current understanding of HFpEF pathophysiology by implicating inadequate functional sympatholysis as an important contributor to reduced exercising muscle blood flow in this patient group.

The cardiovascular response to exercise is largely determined by neurocirculatory control mechanisms that help to raise blood pressure and modulate vascular resistance which, in concert with regional vasodilatory mechanisms, promote blood flow to active muscle and organs. These neurocirculatory control mechanisms include a feedforward mechanism, known as central command, and three feedback mechanisms, namely, 1 ) the baroreflex, 2 ) the exercise pressor reflex, and 3 ) the arterial chemoreflex. The hemodynamic consequences of these control mechanisms result from their influence on the autonomic nervous system and subsequent alterations in cardiac output and vascular resistance. Although stimulation of the baroreflex inhibits sympathetic outflow and facilitates parasympathetic activity, central command, the exercise pressor reflex, and the arterial chemoreflex facilitate sympathetic activation and inhibit parasympathetic drive. Despite considerable understanding of the cardiovascular consequences of each of these mechanisms in isolation, the circulatory impact of their interaction, which occurs when various control systems are simultaneously activated (e.g., during exercise at altitude), has only recently been recognized. Although aging and cardiovascular disease (e.g., heart failure, hypertension) have both been recognized to alter the hemodynamic consequences of these regulatory systems, this review is limited to provide a brief overview on the action and interaction of neurocirculatory control mechanisms in health.

Heart failure with preserved ejection fraction (HFpEF) is characterized by reduced ability to sustain physical activity that may be due partly to disease-related changes in autonomic function that contribute to dysregulated cardiovascular control during muscular contraction. Thus, we used a combination of static handgrip exercise (HG) and postexercise ischemia (PEI) to examine the pressor response to exercise and isolate the skeletal muscle metaboreflex, respectively. Mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), and total peripheral resistance (TPR) were assessed during 2-min of static HG at 30 and 40% of maximum voluntary contraction (MVC) and subsequent PEI in 16 patients with HFpEF and 17 healthy, similarly aged controls. Changes in MAP were lower in patients with HFpEF compared with controls during both 30%MVC (Δ11 ± 7 vs. Δ15 ± 8 mmHg) and 40%MVC (Δ19 ± 14 vs. Δ30 ± 8 mmHg), and a similar pattern of response was evident during PEI (30%MVC: Δ8 ± 5 vs. Δ12 ± 8 mmHg; 40%MVC: Δ13 ± 10 vs. Δ18 ± 9 mmHg) (group effect: P = 0.078 and P = 0.017 at 30% and 40% MVC, respectively). Changes in HR, CO, and TPR did not differ between groups during HG or PEI ( P > 0.05). Taken together, these data suggest a reduced pressor response to static muscle contractions in patients with HFpEF compared with similarly aged controls that may be mediated partly by a blunted muscle metaboreflex. These findings support a disease-related dysregulation in neural cardiovascular control that may reduce an ability to sustain physical activity in HFpEF. NEW & NOTEWORTHY The current investigation has identified a diminution in the exercise-induced rise in arterial blood pressure (BP) that persisted during postexercise ischemia (PEI) in an intensity-dependent manner in patients with heart failure with preserved ejection fraction (HFpEF) compared with older, healthy controls. These findings suggest that the pressor response to exercise is reduced in patients with HFpEF, and this deficit may be mediated, in part, by a blunted muscle metaboreflex, highlighting the consequences of impaired neural cardiovascular control during exercise in this patient group.

There is accumulating evidence for both peripheral vascular dysfunction and impaired functional capacity in patients with heart failure with a preserved ejection fraction (HFpEF). Although derangements in the l-arginine-nitric oxide (l-Arg-NO) pathway are likely to contribute to these aspects of HFpEF pathophysiology, the impact of increased NO substrate on vascular health and physical capacity has not been evaluated in this patient population. Thus, using a single-arm study design, we evaluated the impact of enteral l-citrulline (l-Cit, 6 g/day for 7 days), a precursor for l-Arg biosynthesis, on vascular function [flow-mediated dilation (FMD), reactive hyperemia (RH), and passive limb movement (PLM)], functional capacity [6-min walk test (6MWT)], and biomarkers of l-Arg-NO signaling in 14 patients with HFpEF ( n = 14, 4 M/10 F, 70 ± 10 yr, EF: 66 ± 7%). Compared with baseline (0d), 7 days of l-Cit administration improved FMD (0d: 2.5 ± 1.6%, 7d: 4.5 ± 2.9%), RH (0d: 468 ± 167 mL, 7d: 577 ± 199 mL), PLM blood flow area-under-the-curve (0d: 139 ± 130 mL, 7d: 198 ± 115 mL), and 6MWT distance (0d: 377 ± 27 m, 7d: 397 ± 27 m) ( P < 0.05). An increase in plasma l-Cit (0d: 42 ± 11 µM/L, 7d: 369 ± 201 µM/L), l-Arg (0d: 65 ± 8 µM/L, 7d: 257 ± 25 µM/L), and the ratio of l-Arg to asymmetric dimethylarginine (ADMA) (0d: 136 ± 13 AU, 7d: 481 ± 49 AU) ( P < 0.05) was also observed. Though preliminary in nature, these functional and biomarker assessments demonstrate a potential benefit of l-Cit administration in patients with HFpEF, findings that provide new insight into the mechanisms that govern vascular and physical dysfunction in this patient group. NEW & NOTEWORTHY The current investigation has demonstrated that l-Cit administration may improve brachial artery endothelium-dependent vasodilation, upper and lower limb microvascular function, and physical capacity in patients with HFpEF, highlighting the potential therapeutic potential of interventions targeting the l-Arg-NO signaling cascade to improve outcomes in this patient group.

Remnant cholesterol (RC) and non-high-density lipoprotein cholesterol (non-HDL-C) may contribute to the residual risk for atherosclerotic cardiovascular disease. High cardiorespiratory fitness (CRF) is associated with favorable traditional lipid profiles, but its relation with RC and non-HDL-C remains unclear. We analyzed cross-sectional data on 4,613 healthy men (mean age 49 years). CRF was measured using peak oxygen uptake during incremental exercise testing and categorized into quartiles. RC was estimated as total cholesterol minus HDL-C and low-density lipoprotein cholesterol, and elevated RC was defined as ≥38 mg/100 ml (90 percentile). Non-HDL-C was calculated as total cholesterol minus HDL-C, and high non-HLD-C was defined as ≥190 mg/100 ml. CRF was inversely associated with RC (β -0.31, 95% confidence interval [CI] -0.39 to -0.24) and non-HDL-C (β -0.34, 95% CI -0.57 to -0.11) after adjustment for several risk factors. Each metabolic equivalent increment in CRF was associated with lower odds of having elevated RC (odds ratio [OR] 0.85, 95% CI 0.77 to 0.93) and non-HDL-C (OR 0.93, 95% CI 0.85 to 1.00) in multivariable analysis. Compared with the bottom quartile, the top quartile of CRF had significantly lower odds of elevated RC (OR 0.63, 95% CI 0.45 to 0.88) and non-HDL-C (OR 0.68, 95% CI 0.51 to 0.91). In conclusion, higher CRF was independently associated with lower levels of RC and non-HDL-C and lower odds of the prevalence of elevated RC and non-HDL-C in healthy men., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Achieving healthy vascular aging (HVA) is important for decelerating age-related cardiovascular disease risk. We evaluated the interplay between HVA, cardiorespiratory fitness (CRF), and subclinical atherosclerosis., Methods: We analyzed data on 3722 men who underwent cardiopulmonary exercise testing in a health examination program. HVA was defined as blood pressure <140/90 mm Hg without hypertension and brachial-ankle pulse wave velocity <1266 cm/s. CRF was directly measured by peak oxygen uptake. Subclinical atherosclerosis was defined as coronary artery calcification scores of >0 and ≥100 and a mean carotid artery intima-media thickness (CIMT) >75th percentile for each age group as well as >0.8 mm of CIMT. Separate and joint associations of HVA and CRF with subclinical atherosclerosis were evaluated., Results: Each 1 metabolic equivalent increment in CRF was associated with 23% higher odds for having HVA. HVA was associated with lower odds of coronary artery calcification but not CIMT. CRF modified the association between HVA and CIMT>0.8 mm (interaction: P =0.01); HVA was associated with lower odds of CIMT>0.8 mm in fit men with no significant association between HVA and CIMT>0.8 mm in unfit men. Compared with no HVA and being unfit, HVA and being fit was associated with lower odds of subclinical atherosclerosis, but there was no significant association between HVA and being unfit with subclinical atherosclerosis., Conclusions: HVA and higher CRF are each associated with a lower risk of subclinical atherosclerosis in men. Higher CRF is associated with a higher prevalence of HVA and may modify the association between HVA and subclinical atherosclerosis.

New Findings: What is the central question of this study? Are central and peripheral haemodynamics during handgrip exercise different in young adults 3-4 weeks following infection with of SARS-CoV-2 compared with young healthy adults. What is the main finding and its importance? Exercising heart rate was higher while brachial artery blood flow and vascular conductance were lower in the SARS-CoV-2 compared with the control group. These findings provide evidence for peripheral impairments to exercise among adults with SARS-CoV-2, which may contribute to exercise limitations., Abstract: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can have a profound impact on vascular function. While exercise intolerance may accompany a variety of symptoms associated with SARS-CoV-2 infection, the impact of SARS-CoV-2 on exercising blood flow (BF) remains unclear. Central (photoplethysmography) and peripheral (Doppler ultrasound) haemodynamics were determined at rest and during rhythmic handgrip (HG) exercise at 30% and 45% of maximal voluntary contraction (MVC) in young adults with mild symptoms 25 days after testing positive for SARS-CoV-2 (SARS-CoV-2: n = 8M/5F; age: 21 ± 2 years; height: 176 ± 11 cm; mass: 71 ± 11 kg) and were cross-sectionally compared with control subjects (Control: n = 8M/5F; age: 27 ± 6 years; height: 178 ± 8 cm; mass: 80 ± 25 kg). Systolic blood pressure, end systolic arterial pressure and rate pressure product were higher in the SARS-CoV-2 group during exercise at 45% MVC compared with controls. Brachial artery BF was lower in the SARS-CoV-2 group at both 30% MVC (Control: 384.8 ± 93.3 ml min -1 ; SARS-CoV-2: 307.8 ± 105.0 ml min -1 ; P = 0.041) and 45% MVC (Control: 507.4 ± 109.9 ml min -1 ; SARS-CoV-2: 386.3 ± 132.5 ml min -1 ; P = 0.002). Brachial artery vascular conductance was lower at both 30% MVC (Control: 3.93 ± 1.07 ml min -1  mmHg -1 ; SARS-CoV-2: 3.11 ± 0.98 ml min -1  mmHg -1 ; P = 0.022) and 45% MVC (Control: 4.74 ± 1.02 ml min -1  mmHg -1 ; SARS-CoV-2: 3.46 ± 1.10 ml min -1  mmHg -1 ; P < 0.001) in the SARS-CoV-2 group compared to control group. The shear-induced dilatation of the brachial artery increased similarly across exercise intensities in the two groups, suggesting the decrease in exercising BF may be due to microvascular impairments. Brachial artery BF is attenuated during HG exercise in young adults recently diagnosed with mild SARS-CoV-2, which may contribute to diminished exercise capacity among those recovering from SARS-CoV-2 like that seen in severe cases., (© 2021 The Authors. Experimental Physiology © 2021 The Physiological Society.)

We examined the efficacy of ankle bathing versus aerobic exercise to improve vascular function in young adults who were randomized to aerobic exercise (AE) ( n = 13, 40%-60% of heart rate reserve), ankle bathing (AB) ( n = 15, 43 °C), or a control condition (CON) ( n = 14, ankle bathing, 36 °C) for 40 min. Conduit vessel function [brachial artery flow-mediated dilation (FMD)], carotid and femoral artery blood flow and shear rate (SR), and arterial stiffness [carotid-to-femoral pulse wave velocity (cf-PWV), augmentation index (AIx@75), β-stiffness index, and arterial compliance] were evaluated. Compared with CON, AE and AB increased FMD at 30 min and 90 min (interaction: p  < 0.05); AB decreased carotid artery blood flow and SR at 30 min, while both AE and AB increased femoral artery blood flow and SR at 30 min and 90 min (interaction: p  < 0.05); AE and AB decreased cf-PWV and AIx@75 at 30 min and 90 min (interaction: p  < 0.05); and AE improved both carotid and femoral β-stiffness index and arterial compliance, while AB reduced β-stiffness index and increased arterial compliance only in the femoral artery (interaction: p  < 0.05). These findings suggest that ankle bathing may serve as an alternative strategy for enhancing vascular function. Novelty: We observed similar improvements in conduit vessel function, femoral artery blood flow and shear rate, and arterial stiffness following ankle bathing and acute aerobic exercise in young adults. These findings have identified ankle bathing as a potential therapeutic strategy for enhancing vascular function, which may be particularly relevant for those with limited ability to engage in regular aerobic exercise.

Obesity is now considered a primary comorbidity in heart failure with preserved ejection fraction (HFpEF) pathophysiology, mediated largely by systemic inflammation. Although there is accumulating evidence for a disease-related dysregulation of blood flow during exercise in this patient group, the role of obesity in the hemodynamic response to exercise remains largely unknown. Small muscle mass handgrip (HG) exercise was used to evaluate exercising muscle blood flow in nonobese (BMI < 30 kg/m 2 , n = 14) and obese (BMI > 30 kg/m 2 , n = 40) patients with HFpEF. Heart rate (HR), stroke index (SI), cardiac index (CI), mean arterial pressure (MAP), forearm blood flow (FBF), and vascular conductance (FVC) were assessed during progressive intermittent HG exercise [15%-30%-45% maximal voluntary contraction (MVC)]. Blood biomarkers of inflammation [C-reactive protein (CRP) and interleukin-6 (IL-6)] were also determined. Exercising FBF was reduced in obese patients with HFpEF at all work rates (15%: 304 ± 42 vs. 229 ± 15 mL/min; 30%: 402 ± 46 vs. 300 ± 18 mL/min; 45%: 484 ± 55 vs. 380 ± 23 mL/min, nonobese vs. obese, P = 0.025), and was negatively correlated with BMI ( R = -0.47, P < 0.01). In contrast, no differences in central hemodynamics (HR, SI, CI, and MAP) were found between groups. Proinflammatory biomarkers were markedly elevated in patients with obesity (CRP: 2,133 ± 418 vs. 4,630 ± 590 ng/mL, P = 0.02; IL-6: 2.9 ± 0.3 vs. 5.2 ± 0.7 pg/mL, nonobese vs. obese, P = 0.04), and both biomarkers were positively correlated with BMI (CRP: R = 0.40, P = 0.03; IL-6: R = 0.57, P < 0.01). Together, these findings demonstrate the presence of obesity and an accompanying milieu of systemic inflammation as important factors in the dysregulation of exercising muscle blood flow in patients with HFpEF. NEW & NOTEWORTHY Obesity is the primary comorbid condition in HFpEF pathophysiology, but the role of adiposity on the peripheral circulation is not well understood. The present study identified a 30%-40% reduction in forearm blood flow during handgrip exercise, accompanied by a marked elevation in proinflammatory plasma biomarkers, in obese patients with HFpEF compared with their nonobese counterparts. These findings suggest an exaggerated dysregulation in exercising muscle blood flow associated with the obese HFpEF phenotype.

Coronavirus disease 2019 (COVID-19) is a highly contagious respiratory illness caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that began spreading globally in late 2019. While most cases of COVID-19 present with mild to moderate symptoms, COVID-19 was the third leading cause of mortality in the United States in 2020 and 2021. Though COVID-19 affects individuals of all races and ethnicities, non-Hispanic Black and Hispanic/Latinx populations are facing an inequitable burden of COVID-19 characterized by an increased risk for hospitalization and mortality. Importantly, non-Hispanic Black and Hispanic/Latinx adults have also faced a greater risk of non-COVID-19-related mortality (e.g., from cardiovascular disease/CVD) during the pandemic. Contributors to the racial disparities in morbidity and mortality during the pandemic are multi-factorial as we discuss in our companion article on social determinants of health. However, profound racial variation in the prevalence of CVD and metabolic diseases may serve as a key driver of worse COVID-19-related and non-COVID-19-related health outcomes among racial and ethnic minority groups. Within this review, we provide data emphasizing the inequitable burden of CVD and metabolic diseases among non-Hispanic Black and Hispanic/Latinx populations. We also discuss the pathophysiology of these conditions, with a focus on how aberrant physiological alterations in the context of CVD and metabolic diseases manifest to increase susceptibility to severe COVID-19., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Racial and ethnic-related health disparities in the United States have been intensified by the greater burden of Coronavirus Disease 2019 (COVID-19) in racial and ethnic minority populations. Compared to non-Hispanic White individuals, non-Hispanic Black and Hispanic/Latinx individuals infected by COVID-19 are at greater risk for hospitalization, intensive care unit admission, and death. There are several factors that may contribute to disparities in COVID-19-related severity and outcomes in these minority populations, including the greater burden of cardiovascular and metabolic diseases as discussed in our companion review article. Social determinants of health are a critical, yet often overlooked, contributor to racial and ethnic-related health disparities in non-Hispanic Black and Hispanic/Latinx individuals relative to non-Hispanic White individuals. Thus, the purpose of this review is to focus on the essential role of social factors in contributing to health disparities in chronic diseases and COVID-19 outcomes in minority populations. Herein, we begin by focusing on structural racism as a social determinant of health at the societal level that contributes to health disparities through downstream social level (e.g., occupation and residential conditions) and individual level health behaviors (e.g., nutrition, physical activity, and sleep). Lastly, we conclude with a discussion of practical applications and recommendations for future research and public health efforts that seek to reduce health disparities and overall disease burden., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

[Figure: see text].

Chronic sympathetic nervous system (SNS) overactivity, characteristic of heart failure (HF) with reduced ejection fraction (HFrEF), is associated with poor prognosis and contributes to increased mortality risk. Sacubitril-valsartan is a recently approved, first-in-class, angiotensin receptor neprilysin inhibitor (ARNI) drug that markedly reduces the risks of death from cardiovascular causes and hospitalization for HF in patients with HFrEF, but the physiological mechanisms underlying these benefits are not fully understood. This single-arm, open-label, prospective study sought to test the hypothesis that short-term treatment with sacubitril-valsartan reduces SNS activity, measured directly via muscle sympathetic nerve activity (MSNA), in patients with HFrEF. MSNA, heart rate (HR), and arterial blood pressure (BP) were assessed in stable Class II and III patients with HFrEF (n = 9, 69 ± 8 yrs.; 28.6 ± 3.6 kg/m 2 ) on contemporary, guideline-directed medical treatment who were subsequently started on sacubitril-valsartan. These measurements were repeated after two months of treatment with sacubitril-valsartan. Sacubitril-valsartan reduced MSNA burst frequency (baseline: 43 ± 10 bursts/min; 2-month: 36 ± 10 bursts/min, p = 0.05) and burst incidence (baseline: 68 ± 16 bursts/100 heartbeats; 2-month: 55 ± 16 bursts/100 heartbeats, p = 0.02), while HR and BP were unchanged following the treatment (p > 0.05). These preliminary findings provide new evidence regarding the ability of sacubitril-valsartan to rapidly reduce SNS activity in patients with HFrEF, suggesting the presence of a novel sympathoinhibitory effect of this new drug class., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Competing Interests: Conflict of Interest No potential conflict of interest relevant to this article was reported.

Aims: Although both low socioeconomic status (SES) and poor cardiorespiratory fitness (CRF) are associated with increased chronic disease and heightened mortality, it remains unclear whether moderate-to-high levels of CRF are associated with survival benefits in low SES populations. This study evaluated the hypothesis that SES and CRF predict all-cause mortality and cardiovascular disease mortality and that moderate-to-high levels of CRF may attenuate the association between low SES and increased mortality., Methods: This study included 2368 men, who were followed in the Kuopio Ischaemic Heart Disease Study cohort. CRF was directly measured by peak oxygen uptake during progressive exercise testing. SES was characterized using self-reported questionnaires., Results: During a 25-year median follow-up, 1116 all-cause mortality and 512 cardiovascular disease mortality events occurred. After adjusting for potential confounders, men with low SES were at increased risks for all-cause mortality (hazard ratio 1.49, 95% confidence interval: 1.30-1.71) and cardiovascular disease mortality (hazard ratio1.38, 1.13-1.69). Higher levels of CRF were associated with lower risks of all-cause mortality (hazard ratio 0.54, 0.45-0.64) and cardiovascular disease mortality (hazard ratio 0.53, 0.40-0.69). In joint associations of SES and CRF with mortality, low SES-unfit had significantly higher risks of all-cause mortality (hazard ratio 2.15, 1.78-2.59) and cardiovascular disease mortality (hazard ratio 1.95, 1.48-2.57), but low SES-fit was not associated with a heightened risk of cardiovascular disease mortality (hazard ratio 1.09, 0.80-1.48) as compared with their high SES-fit counterparts., Conclusion: Both SES and CRF were independently associated with subsequent mortality; however, moderate-to-high levels of CRF were not associated with an excess risk of cardiovascular disease mortality in men with low SES., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Introduction: Adults with obesity are at an increased risk of incident hypertension. Regular aerobic exercise is recommended for the prevention and treatment of hypertension, but whether young adults with obesity exhibit impaired postexercise blood pressure (BP) and vascular responses remains unclear., Purpose: We tested the hypothesis that young adults with obesity exhibit attenuated postexercise hypotension (PEH) and postexercise peripheral vasodilation compared with young adults without obesity., Methods: Thirty-six normotensive adults without and with obesity (11 men and 7 women per group) underwent measurements of brachial and central BP, and leg blood flow (Doppler ultrasound) at baseline and at 30, 60, and 90 min after acute 1-h moderate-intensity cycling. Leg vascular conductance (LVC) was calculated as flow/mean arterial pressure., Results: Both groups exhibited similar brachial and central PEH (peak change from baseline, -2 and -4 mm Hg for brachial and central systolic BPs, respectively, for both groups; time effect, P < 0.05). Both groups also exhibited postexercise peripheral vasodilation, assessed via LVC (time effect, P < 0.05), but its overall magnitude was smaller in young adults with obesity (LVC change from baseline, +47% ± 37%, +29% ± 36%, and +20% ± 29%) compared with young adults without obesity (LVC change from baseline, +88% ± 58%, +59% ± 54%, and +42% ± 51%; group effect, P < 0.05)., Conclusions: Although obesity did not impair PEH after acute moderate-intensity exercise, young adults with obesity exhibited smaller postexercise peripheral vasodilation compared with young adults without obesity. Collectively, these findings have identified evidence for obesity-induced alterations in the peripheral vasculature after exercise., (Copyright © 2020 by the American College of Sports Medicine.)

The Prospective comparison of ARNI with angiotensin-converting enzyme inhibitor to Determine Impact on Global Mortality and morbidity in Heart Failure trial identified a marked reduction in the risk of death and hospitalization for heart failure in patients with heart failure with reduced ejection fraction (HFrEF) treated with sacubitril-valsartan (trade name Entresto), but the physiological processes underpinning these improvements are unclear. We tested the hypothesis that treatment with sacubitril-valsartan improves peripheral vascular function, functional capacity, and inflammation in patients with HFrEF. We prospectively studied patients with HFrEF ( n = 11, 10 M/1 F, left ventricular ejection fraction = 27 ± 8%) on optimal, guideline-directed medical treatment who were subsequently prescribed sacubitril-valsartan (open-label, uncontrolled, and unblinded). Peripheral vascular function [brachial artery flow-mediated dilation (FMD, conduit vessel function) and reactive hyperemia (RH, microvascular function)], functional capacity [six-minute walk test (6MWT) distance], and the proinflammatory biomarkers tumor necrosis factor-α (TNF-α) and interleukin-18 (IL-18) were obtained at baseline and at 1, 2, and 3 mo of treatment. %FMD improved after 1 mo of treatment, and this favorable response persisted for months 2 and 3 (baseline: 3.25 ± 1.75%; 1 mo: 5.23 ± 2.36%; 2 mo: 5.81 ± 1.79%; 3 mo: 6.35 ± 2.77%), whereas RH remained unchanged. 6MWT distance increased at months 2 and 3 (baseline: 420 ± 92 m; 1 mo: 436 ± 98 m; 2 mo: 465 ± 115 m; 3 mo: 460 ± 110 m), and there was a sustained reduction in TNF-α (baseline: 2.38 ± 1.35 pg/mL; 1 mo: 2.06 ± 1.52 pg/mL; 2 mo: 1.95 ± 1.34 pg/mL; 3 mo: 1.92 ± 1.37 pg/mL) and a reduction in IL-18 at month 3 (baseline: 654 ± 150 pg/mL; 1 mo: 595 ± 140 pg/mL; 2 mo: 601 ± 176 pg/mL; 3 mo: 571 ± 127 pg/mL). This study provides new evidence for the potential of this new drug class to improve conduit vessel function, functional capacity, and inflammation in patients with HFrEF. NEW & NOTEWORTHY We observed an approximately twofold improvement in conduit vessel function (brachial artery FMD), increased functional capacity (6MWT distance), and a reduction in inflammation (TNF-α and IL-18) following 3 mo of sacubitril-valsartan therapy. These findings provide important new information concerning the physiological mechanisms by which this new drug class provokes favorable changes in HFrEF pathophysiology.

New Findings: What is the central question of this study? We aimed to examine oxidative stress, antioxidant capacity and macro- and microvascular function in response to 30 days of oral antioxidant administration in patients with heart failure with reduced ejection fraction. What is the main finding and its importance? We observed an approximately twofold improvement in macrovascular function, assessed via brachial artery flow-mediated dilatation, and a reduction in oxidative stress after antioxidant administration in patients with heart failure with reduced ejection fraction. The improvement in macrovascular function was reversed 1 week after treatment cessation. These findings have identified the potential of oral antioxidant administration to optimize macrovascular health in this patient group., Abstract: Heart failure with reduced ejection fraction (HFrEF) is characterized by macrovascular dysfunction and elevated oxidative stress that may be mitigated by antioxidant (AOx) administration. In this prospective study, we assessed flow-mediated dilatation (FMD) and reactive hyperaemia responses in 14 healthy, older control participants and 14 patients with HFrEF, followed by 30 days of oral AOx administration (1 g vitamin C, 600 I.U. vitamin E and 0.6 g α-lipoic acid) in the patient group. Blood biomarkers of oxidative stress (malondialdehyde) and AOx capacity (ferric reducing ability of plasma) were also assessed. Patients with HFrEF had a lower %FMD (2.63 ± 1.57%) than control participants (5.62 ± 2.60%), and AOx administration improved %FMD in patients with HFrEF (30 days, 4.90 ± 2.38%), effectively restoring macrovascular function to that of control participants. In a subset of patients, we observed a progressive improvement in %FMD across the treatment period (2.62 ± 1.62, 4.23 ± 2.69, 4.33 ± 2.24 and 4.97 ± 2.56% at days 0, 10, 20 and 30, respectively, n = 12) that was abolished 7 days after treatment cessation (2.99 ± 1.78%, n = 9). No difference in reactive hyperaemia was evident between groups or as a consequence of the AOx treatment. Ferric reducing ability of plasma levels increased (from 6.08 ± 2.80 to 6.70 ± 1.59 mm, day 0 versus 30) and malondialdehyde levels decreased (from 6.81 ± 2.80 to 6.22 ± 2.84 μm, day 0 versus 30) after treatment. These findings demonstrate the efficacy of chronic AOx administration in attenuating oxidative stress, improving AOx capacity and restoring macrovascular function in patients with HFrEF., (© 2020 The Authors. Experimental Physiology © 2020 The Physiological Society.)

Aging increases arterial stiffness, which has a negative impact on cerebral blood flow (CBF) regulation (decreases CBF and increases CBF pulsatility). The association between arterial stiffness and CBF pulsatility may, in part, explain the relationship between elevated blood pressure (BP) fluctuations and end-organ disease with aging. To understand the mechanisms by which large BP alterations influence cerebral blood flow regulation in both young and old, we examined the effects of age on central and cerebral blood flow regulation following an acute hypertensive stimulus [resistance-exercise (RE)]. Measurements were obtained pre and immediately, 5, and 30 min post-RE in young ( n = 35) and older ( n = 26) adults. Measurements included cerebral blood velocity (CBv), CBv pulsatility, central pulse-wave velocity (PWV), beta-stiffness index (β), and carotid blood flow pulsatility. Central hemodynamics and BP were continuously recorded. Mean CBv increased immediately post-RE only in the young and decreased below baseline at 5 min post-RE in both groups (interaction, P < 0.05). Older adults had a greater increase in CBv pulsatility immediately post-RE compared with the young (interaction, P < 0.05). Mean BP was higher and carotid pulsatility was lower in the older group and increased immediately post-RE in both groups ( P < 0.05). PWV increased immediately post-RE ( P < 0.05). There were no changes in β. In conclusion, with aging, greater central arterial stiffness leads to a greater transmission of pulsatile blood velocity from the systemic circulation to the cerebral circulation following an acute hypertensive stress. NEW & NOTEWORTHY Reductions in cerebral blood flow and increases in flow pulsatility with aging are associated to cerebrovascular disease; however, little is known about how an acute hypertensive stimulus effects cerebral blood flow regulation in an aged population. Following the hypertensive stimulus, older adults elicit an attenuated increase in cerebral blood velocity and greater transmission of pulsatile velocity to the brain compared with young adults, demonstrating reduced cerebral blood flow regulation to elevated blood pressure responses with aging.

Purpose: Frequent consumption of high-fat meals and prolonged sedentary time are prevalent lifestyles that have been associated with an increased risk of vascular and metabolic complications. This study evaluated the acute effects of interrupting prolonged sitting with stair climbing on vascular and metabolic function after a high-fat meal., Methods: In a randomized, cross-over trial, 12 healthy adults (age:  23.5 ± 2.9 years) consumed a high-fat meal, followed by either 1) a 4-h uninterrupted sitting (sitting trial) or 2) a 4-h sitting interrupted with a 5-min stair climbing (average intensity: 66% of heart rate reserve) every hour (interrupted trial). Plasma triglyceride and glucose concentrations, as well as popliteal artery blood flow and shear rate were assessed at baseline and every hour after a high-fat meal, whereas brachial artery flow-mediated dilation was assessed at baseline and again at the end of each trial., Results: Plasma triglyceride and glucose concentrations increased after a high-fat meal and returned to baseline at the end of both trials. Following a high-fat meal, brachial artery flow-mediated dilation decreased in the sitting trial, but not in the interrupted trial (sitting trial: 9.65 ± 2.63% to 7.84 ± 2.36%; interrupted trial: 9.41 ± 2.61% to 10.34 ± 3.30%, p = 0.009 for interaction). Compared with the sitting trial, the interrupted trial improved popliteal blood flow and shear rate (p = 0.004 and p = 0.008 for interaction, respectively)., Conclusions: These findings suggest that interrupting prolonged sitting with stair climbing may be an effective lifestyle strategy to prevent against vascular dysfunction that might occur as a result of prolonged sitting after consuming a high-fat meal in young healthy adults.

Key Points: Exercise in patients with hypertension can be accompanied by an abnormal cardiovascular response that includes attenuated blood flow and an augmented pressor response. Endothelin-1, a very potent vasoconstrictor, is a key modulator of blood flow and pressure during in health and has been implicated as a potential cause of the dysfunction in hypertension. We assessed the role of endothelin-1, acting through endothelin A (ET A ) receptors, in modulating the central and peripheral cardiovascular responses to exercise in patients with hypertension via local antagonism of these receptors during exercise. ET A receptor antagonism markedly increased leg blood flow, vascular conductance, oxygen delivery, and oxygen consumption during exercise; interestingly, these changes occurred in the presence of reduced leg perfusion pressure, indicating that these augmentations were driven by changes in vascular resistance. These data indicate that ET A receptor antagonism could be a viable therapeutic approach to improve blood flow during exercise in hypertension., Abstract: Patients with hypertension can exhibit impaired muscle blood flow and exaggerated increases in blood pressure during exercise. While endothelin (ET)-1 plays a role in regulating blood flow and pressure during exercise in health, little is known about the role of ET-1 in the cardiovascular response to exercise in hypertension. Therefore, eight volunteers diagnosed with hypertension were studied during exercise with either saline or BQ-123 (ET A receptor antagonist) infusion following a 2-week withdrawal of anti-hypertensive medications. The common femoral artery and vein were catheterized for drug infusion, blood collection and blood pressure measurements, and leg blood flow was measured by Doppler ultrasound. Patients exercised at both absolute (0, 5, 10, 15 W) and relative (40, 60, 80% peak power) intensities. BQ-123 increased blood flow at rest (79 ± 87 ml/min; P = 0.03) and augmented the exercise-induced hyperaemia at most intensities (80% saline: Δ3818±1222 vs. BQ-123: Δ4812±1469 ml/min; P = 0.001). BQ-123 reduced leg MAP at rest (-8 ± 4 mmHg; P < 0.001) and lower intensities (0-10 W; P < 0.05). Systemic diastolic blood pressure was reduced (0 W, 40%; P < 0.05), but systemic MAP was defended by an increased cardiac output. The exercise pressor response (ΔMAP) did not differ between conditions (80% saline: 25 ± 10, BQ-123: 30 ± 7 mmHg; P = 0.17). Thus, ET-1, acting through the ET A receptors, contributes to the control of blood pressure at rest and lower intensity exercise in these patients. Furthermore, the finding that ET-1 constrains the blood flow response to exercise suggests that ET A receptor antagonism could be a therapeutic approach to improve blood flow during exercise in hypertension., (© 2019 The Authors. The Journal of Physiology © 2019 The Physiological Society.)