Hypoxemia and hypercapnia synergistically mediate peripheral vasoconstriction, whereas hypercapnia mediates cerebral vasodilation in resting humans.

Blacks have the highest prevalence of hypertension, putting them at greater risk of cardiovascular disease and death. Previous studies have reported that, relative to whites, healthy black men have augmented pressor responses to sympathoexcitatory stressors. Although important, these studies do not inform about the resting state and the influence of spontaneous changes in resting muscle sympathetic nerve activity (MSNA). Likewise, little is known about the transduction of MSNA into a vascular response at rest on a beat-to-beat basis. Accordingly, we tested the hypothesis that relative to whites, blacks would exhibit greater vasoconstriction and pressor responses following spontaneous bursts of MSNA. Mean arterial pressure, common femoral artery blood flow, and MSNA were continuously recorded during 20 minutes of supine rest in 35 young healthy men (17 blacks and 18 whites). Signal averaging was used to characterize changes in leg vascular conductance, total vascular conductance, and mean arterial pressure following spontaneous MSNA bursts. Blacks demonstrated significantly greater decreases in leg vascular conductance (blacks: -15.0±1.0%; whites: -11.5±1.2%; P=0.042) and total vascular conductance (blacks: -8.6±0.9%; whites: -5.1±0.4%; P=0.001) following MSNA bursts, which resulted in greater mean arterial pressure increases (blacks: +5.2±0.6 mm Hg; whites: +3.9±0.3 mm Hg; P=0.04). These exaggerated responses in blacks compared with whites were present whether MSNA bursts occurred in isolation (singles) or in combination (multiples) and were graded with increases in burst height. Collectively, these findings suggest that healthy young black men exhibit augmented sympathetic vascular transduction at rest and provide novel insight into potential mechanism(s) by which this population may develop hypertension later in life.

Our aim was to test the hypothesis that apnea-induced hemodynamic responses during dynamic exercise in humans differ between those who show strong bradycardia and those who show only mild bradycardia. After apnea-induced changes in heart rate (HR) were evaluated during dynamic exercise, 23 healthy subjects were selected and divided into a large response group (L group; n = 11) and a small response group (S group; n = 12). While subjects performed a two-legged dynamic knee extension exercise at a work load that increased HR by 30 beats/min, apnea-induced changes in HR, cardiac output (CO), mean arterial pressure (MAP), arterial O(2) saturation (Sa(O(2))), forearm blood flow (FBF), and leg blood flow (LBF) were measured. During apnea, HR in the L group (54 ± 2 beats/min) was lower than in the S group (92 ± 3 beats/min, P < 0.05). CO, Sa(O(2)), FBF, LBF, forearm vascular conductance (FVC), leg vascular conductance (LVC), and total vascular conductance (TVC) were all reduced, and MAP was increased in both groups, although the changes in CO, TVC, LBF, LVC, and MAP were larger in the L group than in the S group (P < 0.05). Moreover, there were significant positive linear relationships between the reduction in HR and the reductions in TVC, LVC, and FVC. We conclude that individuals who show greater apnea-induced bradycardia during exercise also show greater vasoconstriction in both active and inactive muscle regions.

Recent work suggests that β-adrenergic vasodilation offsets α-adrenergic vasoconstriction in young women, but this effect is lost after menopause. Given these age-related vascular changes, we tested the hypothesis that older women would exhibit a greater change in vascular conductance following baroreflex perturbation compared with young women. In 10 young (21 ± 1 yr) and 10 older (62 ± 2 yr) women, mean arterial pressure (MAP; Finometer), heart rate (HR), cardiac output (CO; Modelflow), total vascular conductance (TVC), and leg vascular conductance (LVC, duplex-Doppler ultrasound) were continuously measured in response to 5-s pulses of neck suction (NS; -60 Torr) and neck pressure (NP; +40 Torr) to simulate carotid hypertension and hypotension, respectively. Following NS, decreases in MAP were similar between groups; however, MAP peak response latency was slower in older women (P < 0.05). Moreover, at the time of peak MAP, increases in LVC (young, -11.5 ± 3.9%LVC vs. older, +19.1 ± 7.0%LVC; P < 0.05) and TVC were greater in older women, whereas young women exhibited larger decreases in HR and CO (young, -10 ± 3% CO vs. older, +0.8 ± 2% CO; P < 0.05). Following NP, increases in MAP were blunted (young, +14 ± 1 mmHg vs. older, +8 ± 1 mmHg; P < 0.05) in older women, whereas MAP response latencies were similar. Interestingly, decreases in LVC and TVC were similar between groups, but HR and CO (young, +7.0 ± 2% CO vs. older, -4.0 ± 2% CO; P < 0.05) responses were attenuated in older women. These findings suggest that older women have greater reliance on vascular conductance to modulate MAP via carotid baroreflex, whereas young women rely more on cardiac responsiveness. Furthermore, older women demonstrate a blunted ability to increase MAP to hypotensive stimuli.

Systemic blood distribution is an important factor involved in regulating cerebral blood flow (CBF). However, the effect of an acute change in central blood volume (CBV) on CBF regulation remains unclear. To address our question, we sought to examine the CBF and systemic hemodynamic responses to microgravity during parabolic flight. Twelve healthy subjects were seated upright and exposed to microgravity during parabolic flight. During the brief periods of microgravity, mean arterial pressure was decreased (-26 ± 1%, P < 0.001), despite an increase in cardiac output (+21 ± 6%, P < 0.001). During microgravity, central arterial pulse pressure and estimated carotid sinus pressure increased rapidly. In addition, this increase in central arterial pulse pressure was associated with an arterial baroreflex-mediated decrease in heart rate (r = -0.888, P < 0.0001) and an increase in total vascular conductance (r = 0.711, P < 0.001). The middle cerebral artery mean blood velocity (MCA Vmean) remained unchanged throughout parabolic flight (P = 0.30). During microgravity the contribution of cardiac output to MCA Vmean was gradually reduced (P < 0.05), and its contribution was negatively correlated with an increase in total vascular conductance (r = -0.683, P < 0.0001). These findings suggest that the acute loading of the arterial and cardiopulmonary baroreceptors by increases in CBV during microgravity results in acute and marked systemic vasodilation. Furthermore, we conclude that this marked systemic vasodilation decreases the contribution of cardiac output to CBF. These findings suggest that the arterial and cardiopulmonary baroreflex-mediated peripheral vasodilation along with dynamic cerebral autoregulation counteracts a cerebral overperfusion, which otherwise would occur during acute increases in CBV.

Previous studies in humans attempting to assess sympathetic vascular transduction have related large reflex-mediated increases in muscle sympathetic nerve activity (MSNA) to associated changes in limb vascular resistance. However, such procedures do not provide insight into the ability of MSNA to dynamically control vascular tone on a beat-by-beat basis. Thus we examined the influence of spontaneous MSNA bursts on leg vascular conductance (LVC) and how variations in MSNA burst pattern (single vs. multiple bursts) and burst size may affect the magnitude of the LVC response. In 11 young men, arterial blood pressure, common femoral artery blood flow, and MSNA were continuously recorded during 20 min of supine rest. Signal averaging was used to characterize percent changes in LVC for 15 cardiac cycles following heartbeats associated with and without MSNA bursts. LVC significantly decreased following MSNA bursts, reaching a nadir during the 6th cardiac cycle (single bursts, -2.9 ± 1.1%; and multiple bursts, -11.0 ± 1.4%; both, P < 0.001). Individual MSNA burst amplitudes and the total amplitude of consecutive bursts were related to the magnitude of peak decreases in LVC. In contrast, cardiac cycles without MSNA bursts were associated with a significant increase in LVC (+3.1 ± 0.5%; P < 0.001). Total vascular conductance decreased in parallel with LVC also reaching a nadir around the peak rise in arterial blood pressure following an MSNA burst. Collectively, these data are the first to assess beat-by-beat sympathetic vascular transduction in resting humans, demonstrating robust and dynamic decreases in LVC following MSNA bursts, an effect that was absent for cardiac cycles without MSNA bursts.

We tested the hypothesis that excess cardiac activation (ECA) generates increased cardiovascular circuit flow at the onset of exercise. Thirty participants (14 females) performed 30 s of right-legged knee extension/flexion exercise at 50% of one-legged WRPEAK to assess the normal cardiovascular adjustment at the onset of single-leg exercise (control; CON). ECA in isolation was accomplished in separate trials by initiating exercise with both the right leg and the occluded left leg (each at 50% one-legged WRPEAK) to generate additional muscle mass activation of autonomic cardiac control without allowing the exercising left leg circulation to add to the cardiovascular circuit. Central (finger photoplethysmography) and peripheral (Doppler ultrasound) hemodynamics were measured continuously. ECA increased cardiac activation versus CON (Δ heart rate; 35.3 ± 8.4 vs. 24.5 ± 8.7 beats/min, P < 0.0001), which elevated ΔQ̇ (4.62 ± 1.62 vs. 3.48 ± 1.51 L/min, P < 0.001) as Δ stroke volume was not different between conditions. ECA increased Δ mean arterial pressure (11.9 ± 5.8 vs. 5.5 ± 5.6 mmHg, P < 0.0001) via ΔQ̇, as Δ total vascular conductance was also greater during ECA (36.6 ± 18.3 vs. 31.3 ± 15.1 mL/min/mmHg, P = 0.0120). Δ exercising leg blood flow (LBF; 2,594.3 ± 639.6 vs. 2,425.1 ± 550.9 mL/min, P = 0.0179), but not Δ leg vascular conductance, was greater in ECA vs. CON. These findings demonstrate that excess exercise-induced cardiac activation can create a greater increase in Q̇ and exercising leg perfusion at exercise onset without a change in exercising leg vasodilation magnitude during sub-maximal knee flexion/extension exercise.NEW & NOTEWORTHY Whether increasing cardiac activation above normal can increase cardiovascular circuit blood flow above normal at exercise onset in humans remained unclear. We found that excess exercise-induced cardiac activation created a greater increase in cardiac output via greater heart rate increases. Furthermore, exercising leg perfusion also increased to a greater extent due to elevated arterial blood pressure created by greater cardiac output. In conclusion, increased cardiac activation can improve cardiovascular circuit flow responses at exercise onset.

Dietary nitrate (NO(3)(-)) supplementation, via its reduction to nitrite (NO(2)(-)) and subsequent conversion to nitric oxide (NO) and other reactive nitrogen intermediates, reduces blood pressure and the O(2) cost of submaximal exercise in humans. Despite these observations, the effects of dietary NO(3)(-) supplementation on skeletal muscle vascular control during locomotory exercise remain unknown. We tested the hypotheses that dietary NO(3)(-) supplementation via beetroot juice (BR) would reduce mean arterial pressure (MAP) and increase hindlimb muscle blood flow in the exercising rat. Male Sprague-Dawley rats (3-6 months) were administered either NO(3)(-) (via beetroot juice; 1 mmol kg(-1) day(-1), BR n = 8) or untreated (control, n = 11) tap water for 5 days. MAP and hindlimb skeletal muscle blood flow and vascular conductance (radiolabelled microsphere infusions) were measured during submaximal treadmill running (20 m min(-1), 5% grade). BR resulted in significantly lower exercising MAP (control: 137 ± 3, BR: 127 ± 4 mmHg, P < 0.05) and blood [lactate] (control: 2.6 ± 0.3, BR: 1.9 ± 0.2 mm, P < 0.05) compared to control. Total exercising hindlimb skeletal muscle blood flow (control: 108 ± 8, BR: 150 ± 11 ml min(-1) (100 g)(-1), P < 0.05) and vascular conductance (control: 0.78 ± 0.05, BR: 1.16 ± 0.10 ml min(-1) (100 g)(-1) mmHg(-1), P < 0.05) were greater in rats that received BR compared to control. The relative differences in blood flow and vascular conductance for the 28 individual hindlimb muscles and muscle parts correlated positively with their percentage type IIb + d/x muscle fibres (blood flow: r = 0.74, vascular conductance: r = 0.71, P < 0.01 for both). These data support the hypothesis that NO(3)(-) supplementation improves vascular control and elevates skeletal muscle O(2) delivery during exercise predominantly in fast-twitch type II muscles, and provide a potential mechanism by which NO(3)(-) supplementation improves metabolic control.

The cerebral vasodilator response to increased arterial carbon dioxide (CO2) concentration, termed cerebral vasomotor reactivity (CVMR), is used to assess cerebral vascular function. We sought to assess the within-day and between-day repeatability of CVMR to rebreathing-induced hypercapnia. Twelve healthy adults performed a within-day short interval protocol (17 ± 2 min between trials), ten performed a within-day long interval protocol (145 ± 16 min between trials), and seventeen performed a between-day protocol (5 ± 2 days between visits). Repeatability of the slope of the percent change in middle cerebral artery mean blood velocity (%MCAvmean) and cerebral vascular conductance index (%CVCi), to the change in partial pressure of end-tidal CO2 ([Formula: see text]) between the two trials/days was assessed. Within-day short interval, %MCAvmean slope demonstrated fair to excellent repeatability (intraclass correlation, ICC = 0.92 [95% confidence interval 0.72-0.98]; P < 0.001) while %CVCi slope showed more variability (ICC = 0.84 [0.47-0.95]; P = 0.002]). Within-day long interval, %MCAvmean (ICC = 0.95 [0.80-0.99]) and %CVCi (ICC = 0.94 [0.71-0.99]) slopes showed good to excellent and fair to excellent repeatability respectively (P < 0.001 for both). For between-day trials, better repeatability was observed for %CVCi (ICC = 0.85 [0.57-0.95]; P < 0.001) compared with %MCAvmean (ICC = 0.76 [0.33-0.91]; P = 0.004) slope. These findings indicate repeatable within- and between-day CVMR responses to rebreathe-induced hypercapnia. However, a longer interval may be better for within-day repeat trials, particularly for CVCi measures.NEW & NOTEWORTHY The cerebral vasodilator response to increases in arterial carbon dioxide concentration, termed cerebral vasomotor reactivity, provides an index of cerebral vascular function/health. Reduced responses are present in populations with elevated cerebral vascular and neurocognitive disease risk/overt disease. Cerebral vasomotor reactivity is often assessed during rebreathing-induced hypercapnia. This study determined that the day-to-day and between-day variability in this response is repeatable, thereby providing important methodological information to the scientific community.

BackgroundPost-exercise hypotension (PEH) following prolonged dynamic exercise arises from increased total vascular conductance (TVC) via skeletal muscle vasodilation. However, arterial vasodilation of skeletal musculatures does not entirely account for the rise in TVC. The aim of the present study was to determine the contribution of vascular conductance (VC) of the legs, arms, kidneys and viscera to TVC during PEH.MethodsEight subjects performed a single period of cycling at 60% of heart rate (HR) reserve for 60 minutes. Blood flow in the right renal, superior mesenteric, right brachial and right femoral arteries was measured by Doppler ultrasonography in a supine position before exercise and during recovery. HR and mean arterial pressure (MAP) were measured continuously. MAP decreased significantly from approximately 25 minutes after exercise cessation compared with pre-exercise baseline. TVC significantly increased (approximately 23%; P <0.05) after exercise compared with baseline, which resulted from increased VC in the leg (approximately 33%) and arm (approximately 20%), but not in the abdomen.ConclusionPEH was not induced by decreased cardiac output, but by increased TVC, two-thirds of the rise in which can be attributed to increased VC in active and inactive limbs.

The sympathetic nervous system is important for cardiovascular regulation, particularly during acute stress. Efferent sympathetic outflow can be regulated in an organ-dependent manner, but whether renal and leg vasoconstriction are associated at rest or during sympathetic stressors is unknown. Therefore, we sought to determine the relationships between muscle sympathetic nerve activity (MSNA), leg vascular conductance (LVC), and renal vascular conductance (RVC) at rest and during common laboratory-based sympathoexcitatory stimuli in a cohort of young healthy adults. Beat-to-beat arterial pressure (photoplethysmography), MSNA (microneurography), superficial femoral artery blood flow, and renal artery blood velocity (Doppler ultrasound) were measured at rest and during static handgrip exercise (30% maximal voluntary contraction), postexercise circulatory occlusion (PECO), and cold stress (hand in 3.8 ± 1.3°C water) in 37 young healthy adults (16 females, 21 males). At rest, RVC was unrelated to LVC (r = -0.11, P = 0.55) or MSNA burst frequency (ρ = -0.22, P = 0.26). Static handgrip, PECO, and cold stress each induced an increase in mean arterial pressure and MSNA and a reduction in RVC (all P < 0.001). LVC was unaltered during stress (all P ≥ 0.16), with the exception of a reduction during the second minute of cold stress (P = 0.03). During stress, changes in RVC were not associated with changes in LVC (handgrip: r = -0.24, P = 0.21; PECO: ρ = -0.04, P = 0.82; cold stress: r = -0.17, P = 0.38) or MSNA (handgrip: ρ = -0.14, P = 0.48; PECO: r = 0.27, P = 0.15; cold stress: r = -0.27, P = 0.16). Furthermore, MSNA was not associated with LVC at rest or during stress (all P ≥ 0.12). The present findings highlight the differential control of regional sympathetic vasoconstriction at rest and during stress in young healthy humans.NEW & NOTEWORTHY The sympathetic nervous system plays a critical role in cardiovascular regulation at rest and during stress. We demonstrate that renal artery vascular conductance is unrelated to superficial femoral artery vascular conductance or muscle sympathetic nerve activity at rest or during laboratory-based sympathetic stressors in young healthy adults. These findings support the concept of differential control of peripheral sympathetic outflow at rest and during stress in humans.

Obesity has been associated with a slowing of V˙O2 dynamics in children and adolescents, but this problem has not been studied in adults. Cardiovascular mechanisms underlying this effect are not clear. In this study, 48 adults (18 males, 30 females) grouped according to body mass index (BMI) (lean < 25 kg·m−2, overweight = 25–29.9 kg·m−2, obese ≥30 kg·m−2) provided a fasting blood sample, completed a maximal graded exercise test and six bouts of submaximal exercise on a cycle ergometer, and performed two protocols of calf exercise. Dynamic response characteristics of V˙O2 and leg vascular conductance (LVC) were assessed during cycling (80% ventilatory threshold) and calf exercise (30% MVC), respectively. Dynamic responses of cardiac output, mean arterial pressure and total systemic vascular conductance were also assessed during cycling based on measurements at 30 and 240 sec. The time constant of the second phase of the V˙O2 response was significantly greater in obese than lean subjects (39.4 (9.2) vs. 29.1 (7.6) sec); whereas dynamic responses of cardiac output and systemic vascular conductance were not affected by BMI. For calf exercise, the time constant of the second growth phase of LVC was slowed significantly in obese subjects (22.1 (12.7) sec) compared with lean and overweight subjects (11.6 (4.5) sec and 13.4 (6.7) sec). These data show that obesity slows dynamic responses of V˙O2 during cycling and the slower phase of vasodilation in contracting muscles of male and female adults.

Post-exercise hypotension (PEH) is a sustained reduction in mean arterial blood pressure (MAP) after prolonged exercise. As water drinking is known to elicit a large acute pressor response, we aimed to explore the effect of drinking water during exercise on PEH. Ten normotensive male volunteers performed the control protocol: 30 min supine rest, 60 min cycling exercise in moderate intensity, and 60 min supine rest recovery. In the water drinking protocol, the same procedure was followed but with water intake during exercise to compensate for exercise-induced body weight lost. Heart rate, MAP, cardiac output and blood flow in the brachial artery were measured pre- and post-exercise. The total vascular conductance (TVC) and the vascular conductance (VC) in the brachial artery were calculated pre- and post-exercise, and the relative change in plasma volume (ΔPV) was also measured. Body weight loss during exercise was 0.65 ± 0.24 kg in the control. ΔPV was not different during recovery in either protocol. MAP in the control was significantly reduced during the latter half of the recovery compared with baseline. In contrast, MAP in the water drinking showed no reduction during recovery, and was significantly higher than in the control. TVC and VC in the brachial artery were lower in the water drinking, in which vasoconstriction was relatively exaggerated. Prevention of dehydration after exercise by oral water intake, or oral water intake per se has a role in maintaining post-exercise MAP and it may be related to reduction in TVC.

Chronic heart failure (CHF) results in central and peripheral derangements that ultimately reduce skeletal muscle O2 delivery and impair exercise tolerance. Dietary nitrate (NO3‐) supplementation improves skeletal muscle vascular function and improves tolerance to exercise. We tested the hypothesis that NO3‐ supplementation would elevate exercising skeletal muscle blood flow (BF) and vascular conductance (VC) in CHF rats. Myocardial infarction (MI) was induced (coronary artery ligation) in young‐adult male rats. After 21‐days of recovery, rats randomly received NO3‐ rich beetroot juice (CHF+BR, n=10) or a placebo (CHF, n=10). Mean arterial pressure (MAP, carotid artery catheter) and skeletal muscle BF (radiolabeled microspheres) was measured during treadmill exercise (20 m/min, 5% grade). CHF parameters (MI size, CHF: 29 ± 3, CHF+BR: 33 ± 4%, LVEDP, CHF: 18 ± 2, CHF+BR: 18 ± 2 mmHg) and exercising MAP (CHF: 131 ± 3, CHF +BR: 128 ± 4 mmHg) were not different (P&lt;0.05) between groups. Total hindlimb skeletal muscle BF (CHF: 95 ± 5, CHF+BR: 116 ± 9 ml/min/100g) and VC (CHF: 0.75 ± 0.05, CHF+BR: 0.90 ± 0.05) were greater (P&lt;0.05) in BR supplemented rats. The increases in BF and VC (P&lt;0.05) were found preferentially in muscles and muscle parts containing 蠅70% type IIb + d/x muscle fibers which resulted in a ~22% increase in total skeletal muscle BF and a 20% increase in total VC during exercise. These results provide strong evidence that dietary NO3‐ supplementation improves skeletal muscle vascular function during exercise in rats with CHF and suggest that BR may provide a novel therapeutic modality for the treatment of CHF.&#x0D; NIH HL‐108328

The effect of antihypertensive drugs on autonomic neural control of the cerebral circulation remains unclear. This study was designed to compare middle cerebral artery mean blood velocity responses to acute hypotension with and without alpha(1)-adrenoreceptor blockade (Prazosin) in young, healthy humans. Acute hypotension was induced nonpharmacologically in 6 healthy subjects (mean+/-SE; 28+/-2 years) by releasing bilateral thigh cuffs after 9 minutes of suprasystolic resting ischemia before and after an oral dose of Prazosin (1 mg/20 kg body weight). Prazosin had no effect on thigh cuff release-induced reductions in mean arterial pressure and middle cerebral artery mean blood velocity. However, Prazosin attenuated the amount of peripheral vasoconstriction through the arterial baroreflex as evidenced by a slower return of mean arterial pressure to baseline (P=0.03). Immediately after cuff release, cerebral vascular conductance index increased through cerebral autoregulation and returned to resting values as a result of an increased perfusion pressure mediated through arterial baroreflex mechanisms. The rate of regulation, an index of cerebral autoregulation, was attenuated with Prazosin (control versus Prazosin; rate of regulation=0.204+/-0.020 versus 0.006+/-0.053/s, P=0.037). In addition, as mean arterial pressure was returning to resting values, the rate of change in cerebral vascular conductance index was decreased with Prazosin (0.005+/-0.006/s) compared with control (0.025+/-0.005/s; P=0.010). These data suggest that during recovery from acute hypotension, decreases in cerebral vascular conductance index were mediated by increases in arterial blood pressure and sympathetically mediated cerebral vasoconstriction.

BackgroundRecently, it was reported in healthy young subjects that fructose containing drinks increased blood pressure acutely, without any apparent change in total vascular conductance (TVC). However, because it is well known that the splanchnic vasculature is dilated by oral fructose ingestion, it is assumed to be the concomitant vasoconstriction in other peripheral region(s) that is responsible for this finding. Thus, the purpose of this study was to determine the acute response of regional VC to oral fructose ingestion in young healthy humans.ResultsIn 12 healthy young subjects, mean arterial blood pressure (MAP), heart rate, cardiac output, and blood flow (BF) in the superior mesenteric (SMA), brachial (BA), and popliteal (PA) arteries, in addition to forearm skin BF, were measured continuously for 2 h after ingestion of 400 ml fructose solution (containing 50 g fructose). Regional VC was calculated as BF/MAP. MAP increased for 120 min after fructose ingestion without any change in TVC. While VC in the SMA was elevated after ingestion, VC in BA and PA and forearm skin decreased.ConclusionsWhile TVC was apparently unchanged during the 2 h after fructose ingestion, there were coincident changes in regional VCs in the peripheral circulation, but no net change in TVC.