Regional hemodynamics during postexercise hypotension. I. Splanchnic and renal circulations.

Moderate exercise elicits a relative postexercise hypotension that is caused by an increase in systemic vascular conductance. Previous studies have shown that skeletal muscle vascular conductance is increased postexercise. It is unclear whether these hemodynamic changes are limited to skeletal muscle vascular beds. The aim of this study was to determine whether the splanchnic and/or renal vascular beds also contribute to the rise in systemic vascular conductance during postexercise hypotension. A companion study aims to determine whether the cutaneous vascular bed is involved in postexercise hypotension (Wilkins BW, Minson CT, and Halliwill JR. J Appl Physiol 97: 2071-2076, 2004). Heart rate, arterial pressure, cardiac output, leg blood flow, splanchnic blood flow, and renal blood flow were measured in 13 men and 3 women before and through 120 min after a 60-min bout of exercise at 60% of peak oxygen uptake. Vascular conductances of leg, splanchnic, and renal vascular beds were calculated. One hour postexercise, mean arterial pressure was reduced (79.1 +/- 1.7 vs. 83.4 +/- 1.8 mmHg; P < 0.05), systemic vascular conductance was increased by approximately 10%, leg vascular conductance was increased by approximately 65%, whereas splanchnic (16.0 +/- 1.8 vs. 18.5 +/- 2.4 ml.min(-1).mmHg(-1); P = 0.13) and renal (20.4 +/- 3.3 vs. 17.6 +/- 2.6 ml.min(-1).mmHg(-1); P = 0.14) vascular conductances were unchanged compared with preexercise. This suggests there is neither vasoconstriction nor vasodilation in the splanchnic and renal vasculature during postexercise hypotension. Thus the splanchnic and renal vascular beds neither directly contribute to nor attenuate postexercise hypotension.     

Cutaneous active vasodilation in humans during passive heating postexercise.

The hypothesis that exercise causes an increase in the postexercise esophageal temperature threshold for onset of cutaneous vasodilation through an alteration of active vasodilator activity was tested in nine subjects. Increases in forearm skin blood flow and arterial blood pressure were measured and used to calculate cutaneous vascular conductance at two superficial forearm sites: one with intact alpha-adrenergic vasoconstrictor activity (untreated) and one infused with bretylium tosylate (bretylium treated). Subjects remained seated resting for 15 min (no-exercise) or performed 15 min of treadmill running at either 55, 70, or 85% of peak oxygen consumption followed by 20 min of seated recovery. A liquid-conditioned suit was used to increase mean skin temperature ( approximately 4.0 degrees C/h), while local forearm temperature was clamped at 34 degrees C, until cutaneous vasodilation. No differences in the postexercise threshold for cutaneous vasodilation between untreated and bretylium-treated sites were observed for either the no-exercise or exercise trials. Exercise resulted in an increase in the postexercise threshold for cutaneous vasodilation of 0.19 +/- 0.01, 0.39 +/- 0.02, and 0.53 +/- 0.02 degrees C above those of the no-exercise resting values for the untreated site (P < 0.05). Similarly, there was an increase of 0.20 +/- 0.01, 0.37 +/- 0.02, and 0.53 +/- 0.02 degrees C for the treated site for the 55, 70, and 85% exercise trials, respectively (P < 0.05). It is concluded that reflex activity associated with the postexercise increase in the onset threshold for cutaneous vasodilation is more likely mediated through an alteration of active vasodilator activity rather than through adrenergic vasoconstrictor activity.     

Changes in regional cerebral blood flow distribution during postexercise hypotension in humans.

This investigation compared patterns of regional cerebral blood flow (rCBF) during exercise recovery both with and without postexercise hypotension (PEH). Eight subjects were studied on 3 days with randomly assigned conditions: 1) after 30 min of rest; 2) after 30 min of moderate exercise (M-Ex) at 60-70% heart rate (HR) reserve during PEH; and 3) after 30 min of light exercise (L-Ex) at 20% HR reserve with no PEH. Data were collected for HR, mean blood pressure (MBP), and ratings of perceived exertion and relaxation, and rCBF was assessed by use of single-photon-emission computed tomography. With the use of ANOVA across conditions, there were differences (P < 0.05; mean +/- SD) from rest during exercise recovery from M-Ex (HR = +12 +/- 3 beats/min; MBP = -9 +/- 2 mmHg), but not from L-Ex (HR = +2 +/- 2 beats/min; MBP = -2 +/- 2 mmHg). After M-Ex, there were decreases (P < 0.05) for the anterior cingulate (-6.7 +/- 2%), right and left inferior thalamus (-10 +/- 3%), right inferior insula (-13 +/- 3%), and left inferior anterior insula (-8 +/- 3%), not observed after L-Ex. There were rCBF decreases for leg sensorimotor regions after both M-Ex (-15 +/- 4%) and L-Ex (-12 +/- 3%) and for the left superior anterior insula (-7 +/- 3% and -6 +/- 3%), respectively. Data show that there are rCBF reductions within specific regions of the insular cortex and anterior cingulate cortex coupled with a postexercise hypotensive response after M-Ex. Findings suggest that these cerebral cortical regions, previously implicated in cardiovascular regulation during exercise, may also be involved in PEH.     

H2-receptor-mediated vasodilation contributes to postexercise hypotension.

The early (approximately 30 min) postexercise hypotension response after a session of aerobic exercise is due in part to H1-receptor-mediated vasodilation. The purpose of this study was to determine the potential contribution of H2-receptor-mediated vasodilation to postexercise hypotension. We studied 10 healthy normotensive men and women (ages 23.7 +/- 3.4 yr) before and through 90 min after a 60-min bout of cycling at 60% peak O2 uptake on randomized control and H2-receptor antagonist days (300 mg oral ranitidine). Arterial pressure (automated auscultation), cardiac output (acetylene washin) and femoral blood flow (Doppler ultrasound) were measured. Vascular conductance was calculated as flow/mean arterial pressure. Sixty minutes postexercise on the control day, femoral (delta62.3 +/- 15.6%, where Delta is change; P < 0.01) and systemic (delta13.8 +/- 5.3%; P = 0.01) vascular conductances were increased, whereas mean arterial pressure was reduced (Delta-6.7 +/- 1.1 mmHg; P < 0.01). Conversely, 60 min postexercise with ranitidine, femoral (delta9.4 +/- 9.2%; P = 0.34) and systemic (delta-2.8 +/- 4.8%; P = 0.35) vascular conductances were not elevated and mean arterial pressure was not reduced (delta-2.2 +/- 1.3 mmHg; P = 0.12). Furthermore, postexercise femoral and systemic vascular conductances were lower (P < 0.05) and mean arterial pressure was higher (P = 0.01) on the ranitidine day compared with control. Ingestion of ranitidine markedly reduces vasodilation after exercise and blunts postexercise hypotension, suggesting H2-receptor-mediated vasodilation contributes to postexercise hypotension.     

Influence of endurance exercise training status and gender on postexercise hypotension.

In sedentary individuals, postexercise hypotension after a single bout of aerobic exercise is due to a peripheral vasodilation. Endurance exercise training has the potential to modify this response and perhaps reduce the degree of postexercise hypotension. We tested the hypothesis that endurance exercise-trained men and women would have blunted postexercise hypotension compared with sedentary subjects but that the mechanism of hypotension would be similar (i.e., vasodilation). We studied 16 endurance-trained and 16 sedentary men and women. Arterial pressure, cardiac output, and total peripheral resistance were determined before and after a single 60-min bout of exercise at 60% peak oxygen consumption. All groups exhibited a similar degree of postexercise hypotension (approximately 4-5 mmHg; P < 0.05 vs. preexercise). In sedentary men and women, hypotension was the result of vasodilation (Deltaresistance: -8.9 +/- 2.2%). In endurance-trained women, hypotension was also the result of vasodilation (-8.1 +/- 4.1%). However, in endurance-trained men, hypotension was the result of a reduced cardiac output (-5.2 +/- 2.4%; P < 0.05 vs. all others) and vasodilation was absent (-0.7 +/- 3.3%; P < 0.05 vs. all others). Thus we conclude the magnitude of postexercise hypotension is similar in sedentary and endurance-trained men and women but that endurance-trained men and women achieve this fall in pressure via different mechanisms.     

Effect of systemic nitric oxide synthase inhibition on postexercise hypotension in humans.

An acute bout of aerobic exercise results in a reduced blood pressure that lasts several hours. Animal studies suggest this response is mediated by increased production of nitric oxide. We tested the extent to which systemic nitric oxide synthase inhibition [N(G)-monomethyl-L-arginine (L-NMMA)] can reverse the drop in blood pressure that occurs after exercise in humans. Eight healthy subjects underwent parallel experiments on 2 separate days. The order of the experiments was randomized between sham (60 min of seated upright rest) and exercise (60 min of upright cycling at 60% peak aerobic capacity). After both sham and exercise, subjects received, in sequence, systemic alpha-adrenergic blockade (phentolamine) and L-NMMA. Phentolamine was given first to isolate the contribution of nitric oxide to postexercise hypotension by preventing reflex changes in sympathetic tone that result from systemic nitric oxide synthase inhibition and to control for alterations in resting sympathetic activity after exercise. During each condition, systemic and regional hemodynamics were measured. Throughout the study, arterial pressure and vascular resistances remained lower postexercise vs. postsham despite nitric oxide synthase inhibition (e.g., mean arterial pressure after L-NMMA was 108.0+/-2.4 mmHg postsham vs. 102.1+/-3.3 mmHg postexercise; P<0.05). Thus it does not appear that postexercise hypotension is dependent on increased production of nitric oxide in humans.     

Effects of the menstrual cycle and sex on postexercise hemodynamics

Factors associated with the menstrual cycle, such as the endogenous hormones estrogen and progesterone, have dramatic effects on cardiovascular regulation. It is unknown how this affects postexercise hemodynamics. Therefore, we examined the effects of the menstrual cycle and sex on postexercise hemodynamics. We studied 14 normally menstruating women [24.0 (4.2) yr; SD] and 14 men [22.5 (3.5) yr] before and through 90 min after cycling at 60% .VO2(peak) for 60 min. Women were studied during their early follicular, ovulatory, and mid-luteal phases; men were studied once. In men and women during all phases studied, mean arterial pressure was decreased after exercise throughout 60 min (P < 0.001) postexercise and returned to preexercise values at 90 min (P = 0.089) postexercise. Systemic vascular conductance was increased following exercise in both sexes throughout 60 min (P = 0.005) postexercise and tended to be elevated at 90 min postexercise (P = 0.052), and femoral vascular conductance was increased following exercise throughout 90 min (P < 0.001) postexercise. Menstrual phase and sex had no effect on the percent reduction in arterial pressure (P = 0.360), the percent rise in systemic vascular conductance (P = 0.573), and the percent rise in femoral vascular conductance (P = 0.828) from before to after exercise, nor did the pattern of these responses differ across recovery with phase or sex. This suggests that postexercise hemodynamics are largely unaffected by sex or factors associated with the menstrual cycle.     

Proton circulation during the photocycle of sensory rhodopsin II.

Sensory rhodopsin II (SRII) in Halobacterium salinarum membranes is a phototaxis receptor that signals through its bound transducer HtrII for avoidance of blue-green light. In the present study we investigated the proton movements during the photocycle of SRII in the HtrII-free and HtrII-complexed form. We monitored sustained light-induced pH changes with a pH electrode, and laser flash-induced pH changes with the pH indicator pyranine using sealed membrane vesicles and open sheets containing the free or the complexed receptor. The results demonstrated that SRII takes up a proton in M-to-O conversion and releases it during O-decay. The uptake and release are from and to the extracellular side, and therefore SRII does not transport the proton across the membrane. The pH dependence of the SRII photocycle indicated the presence of a protonatable group (pK(a) approximately 7.5) in the extracellular proton-conducting path, which plays a role in proton uptake by the Schiff base in the M-to-O conversion. The extracellular proton circulation produced by SRII was not blocked by HtrII complexation, unlike the cytoplasmic proton conduction in SRI that was found in the same series of measurements to be blocked by its transducer, HtrI. The implications of this finding for current models of SRI and SRII signaling are discussed.     

Hemodynamic and autonomic correlates of postexercise hypotension in patients with mild hypertension

We investigated the interplay of neural and hemodynamic mechanisms in postexercise hypotension (PEH) in hypertension. In 15 middle-aged patients with mild essential hypertension, we evaluated blood pressure (BP), cardiac output (CO), total peripheral resistance (TPR), forearm (FVR) and calf vascular resistance (CVR), and autonomic function [by spectral analysis of R-R interval and BP variabilities and spontaneous baroreflex sensitivity (BRS)] before and after maximal exercise. Systolic and diastolic BP, TPR, and CVR were significantly reduced from baseline 60-90 min after exercise. CO, FVR, and HR were unchanged. The low-frequency (LF) component of BP variability increased significantly after exercise, whereas the LF component of R-R interval variability was unchanged. The overall change in BRS was not significant after exercise vs. baseline, although a significant, albeit small, BRS increase occurred in response to hypotensive stimuli. These findings indicate that in hypertensive patients, PEH is mediated mainly by a peripheral vasodilation, which may involve metabolic factors linked to postexercise hyperemia in the active limbs. The vasodilator effect appears to override a concomitant, reflex sympathetic activation selectively directed to the vasculature, possibly aimed to counter excessive BP decreases. The cardiac component of arterial baroreflex is reset during PEH, although the baroreflex mechanisms controlling heart period appear to retain the potential for greater opposition to hypotensive stimuli.     

Lipid oxidation in fit young adults during postexercise recovery.

To evaluate the hypothesis that lipid oxidation predominates in postexercise recovery, we examined healthy men (n = 6; age = 21.2 +/- 0.6 yr) and women (n = 6; age = 22.8 +/- 2.1 yr) during and after two exercise tasks [89 min at 45% and 60 min at 65% of peak rate of oxygen consumption (V(O2 peak))] as well as a time-matched resting control trial (Con). Exercise bouts were matched for energy expenditure. Respiratory exchange ratios (RER) during exercise at 65% V(O2 peak) for both men and women (0.95 +/- 0.01 and 0.93 +/- 0.02) were significantly higher than 45% V(O2 peak) (0.89 +/- 0.01 and 0.86 +/- 0.02) and Con trials (0.86 +/- 0.01 and 0.86 +/- 0.02, respectively). During recovery, for men RER values were 0.78 +/- 0.01 and 0.76 +/- 0.01 after 45% and 65% exercise, respectively. For women, values were 0.79 +/- 0.01 and 0.78 +/- 0.01. These were significantly lower than during both the preexercise resting period and the corresponding no-exercise Con period (0.82 +/- 0.01 and 0.83 +/- 0.01, mean RER for men and women, respectively). Hence, the contribution of lipid oxidation to energy supply increased significantly during recovery compared with preexercise levels, and it was greater after exercise than during the time-matched, no-exercise Con period. It is concluded that, although carbohydrate is the major fuel source during moderate- to high-intensity exercise, 1) there is substantial postexercise lipid oxidation; and 2) lipid oxidation is the same during postexercise recovery whether the relative power output is 45% or 65% of V(O2 peak) when energy expenditure of exercise is matched.     

Regional heterogeneity of myocardial blood flow within the rabbit left ventricle during haemorrhagic hypotension.

Several studies have reported an extensive regional heterogeneity in myocardial blood flow. The reported coefficients of variation for regional myocardial perfusion range from about 0.2 to 0.4 in normotensive animals. The spatial distribution of myocardial perfusion during haemorrhagic hypotension seems not to have been assessed. The goal of the present study was to determine the regional heterogeneity in myocardial blood flow within the rabbit left ventricle during normal conditions and after haemorrhagic hypotension. Radioactive microspheres were infused into the left ventricle in barbiturate anaesthetized rabbits over either 30 or 120 sec. The haemorrhagic hypotension was induced by bleeding, so that mean arterial blood pressure was reduced to about 50% of control. The left ventricles were divided into samples of about 0.025 g each. Regional heterogeneity in the blood flow was expressed as the coefficient of variation corrected for the Poisson distribution of microspheres (CVc). The CVc was 0.37 +/- 0.09 (mean +/- SD) during control and 0.41 +/- 0.11 after bleeding, the CVc obtained after bleeding being somewhat higher than during control (P < 0.05). We obtained a high correlation coefficient (tau about 0.68) between regional perfusion values at control and after bleeding which indicates a stable perfusion pattern within the myocardium. We conclude that the regional distribution of coronary blood flow within the left ventricle is markedly heterogenous during control condition and that this pattern is not changed during haemorrhagic hypotension.     

Cerebral hemodynamics during microgravity.

As one of the causes of the space adaptation syndrome, an increased intracranial pressure due to the cephalad fluid shift is suggested. In the present study, we measured intracranial pressure (ICP), aortic pressure and cerebral flow velocity (CFV) in anesthetized rats (n=5) during 4.5 sec of microgravity induced by free drop. The rats were set at horizontal prone (Flat) and 30-degree head-up whole body tilting (HU) positions to examine the effect of gravitational pressure gradient. Then, arterial pressure at the eye level (APeye), cerebral perfusion pressure (CPP; CPP=APeye-ICP), and CPP-CFV relationship was calculated. In HU position, ICP, APeye, and CPP increased by 2.2 +/- 0.4, 12.3 +/- 2.0, and 10.1 +/- 1.7 mmHg respectively. However, CFV did not change significantly. In Flat position, none of these variables did not change significantly. In HU position the slope of CPP-CFV relationship decreased, suggesting the increased cerebral flow resistance. However, it did not change in Flat position. These results can be understood by the disappearance of gravitational pressure gradient by microgravity and the cerebral autoregulation.     

GABA(A) receptor activation at medullary sympathetic neurons contributes to postexercise hypotension

A single bout of exercise results in a postexercise hypotension (PEH) that is accompanied by a reduced baroreflex function. Based on the role of rostral ventrolateral medulla (RVLM) neurons in controlling sympathetic nerve activity (SNA) and blood pressure, the role of gamma-aminobutyric acid (GABA) in controlling RVLM neuronal activity, and the reduced baroreflex-SNA relationship during PEH, we determined whether: 1) RVLM neuronal activity is decreased during PEH, 2) GABA(A)-receptor mechanisms mediate the decrease, and 3) baroreflex control of RVLM activity is reduced. Spontaneously hypertensive rats (SHR) were subjected to 40 min of treadmill or sham exercise (Sham PEH). PEH lasted 10 h in conscious and anesthetized SHR, indicating that the anesthetics did not affect the expression of PEH. Extracellular RVLM neuronal activity having a cardiac and sympathetic rhythm, lumbar SNA, and blood pressure were recorded at rest and during baroreflex function curves. Resting RVLM neuronal activity was lower and was increased to a greater extent by GABA(A)-receptor antagonism in PEH versus Sham PEH (P < 0.05). Baroreflex control of RVLM neuronal activity operated with a reduced gain (P < 0.05). Thus increased GABA signaling at RVLM neurons may contribute to PEH.