Role of skin blood flow and sweating rate in exercise thermoregulation after bed rest.

Two potential mechanisms, reduced skin blood flow (SBF) and sweating rate (SR), may be responsible for elevated intestinal temperature (T(in)) during exercise after bed rest and spaceflight. Seven men underwent 13 days of 6 degrees head-down bed rest. Pre- and post-bed rest, subjects completed supine submaximal cycle ergometry (20 min at 40% and 20 min at 65% of pre-bed rest supine peak exercise capacity) in a thermoneutral room. After bed rest, T(in) was elevated at rest (+0.31 +/- 0.12 degrees C) and at the end of exercise (+0.33 +/- 0.07 degrees C). Percent increase in SBF during exercise was less after bed rest (211 +/- 53 vs. 96 +/- 31%; P < or = 0.05), SBF/T(in) threshold was greater (37.09 +/- 0.16 vs. 37.33 +/- 0.13 degrees C; P < or = 0.05), and slope of SBF/T(in) tended to be reduced (536 +/- 184 vs. 201 +/- 46%/ degrees C; P = 0.08). SR/T(in) threshold was delayed (37.06 +/- 0.11 vs. 37.34 +/- 0.06 degrees C; P < or = 0.05), but the slope of SR/T(in) (3.45 +/- 1.22 vs. 2.58 +/- 0.71 mg x min-1 x cm-2 x degrees C-1) and total sweat loss (0.42 +/- 0.06 vs. 0.44 +/- 0.08 kg) were not changed. The higher resting and exercise T(in) and delayed onset of SBF and SR suggest a centrally mediated elevation in the thermoregulatory set point during bed rest exposure.     

Effects of mode of exercise recovery on thermoregulatory and cardiovascular responses.

To identify the effects of exercise recovery mode on cutaneous vascular conductance (CVC) and sweat rate, eight healthy adults performed two 15-min bouts of upright cycle ergometry at 60% of maximal heart rate followed by either inactive or active (loadless pedaling) recovery. An index of CVC was calculated from the ratio of laser-Doppler flux to mean arterial pressure. CVC was then expressed as a percentage of maximum (%max) as determined from local heating. At 3 min postexercise, CVC was greater during active recovery (chest: 40 +/- 3, forearm: 48 +/- 3%max) compared with during inactive recovery (chest: 21 +/- 2, forearm: 25 +/- 4%max); all P < 0.05. Moreover, at the same time point sweat rate was greater during active recovery (chest: 0.47 +/- 0.10, forearm: 0.46 +/- 0.10 mg x cm(-2) x min(-1)) compared with during inactive recovery (chest: 0.28 +/- 0.10, forearm: 0.14 +/- 0.20 mg x cm(-2) x min(-1)); all P < 0.05. Mean arterial blood pressure, esophageal temperature, and skin temperature were not different between recovery modes. These data suggest that skin blood flow and sweat rate during recovery from exercise may be modulated by nonthermoregulatory mechanisms and that sustained elevations in skin blood flow and sweat rate during mild active recovery may be important for postexertional heat dissipation.     

Selected contribution: Gender differences in the endothelin-B receptor contribution to basal cutaneous vascular tone in humans.

To test whether the contribution of endothelin-B (ET-B) receptors to resting vascular tone differs between genders, we administered the ET-B receptor antagonist BQ-788 into the forearm skin of 11 male and 11 female subjects by intradermal microdialysis. Skin blood flow was measured using laser-Doppler flowmetry at the microdialysis site. The probe was perfused with Ringer solution alone, followed by BQ-788 (150 nM) and finally sodium nitroprusside (28 mM) to effect maximal cutaneous vasodilation. Cutaneous vascular conductance (CVC) was calculated (laser-Doppler flowmetry/mean arterial pressure) and normalized to maximal levels (%max). In male subjects, baseline CVC was (mean +/- SE) 19 +/- 3%max and increased to 26 +/- 5%max with BQ-788 (P < 0.05 vs. baseline). In female subjects, baseline CVC was 13 +/- 1%max and decreased to 10 +/- 1%max in response to BQ-788. CVC responses to BQ-788 differed with gender (P < 0.05); thus the contribution of ET-B receptors to resting cutaneous vascular tone differs between men and women. In men, ET-B receptors mediate tonic vasoconstriction, whereas, in women, ET-B receptors mediate tonic vasodilation.     

Prolonged head-down tilt exposure reduces maximal cutaneous vasodilator and sweating capacity in humans.

Cutaneous vasodilation and sweat rate are reduced during a thermal challenge after simulated and actual microgravity exposure. The effects of microgravity exposure on cutaneous vasodilator capacity and on sweat gland function are unknown. The purpose of this study was to test the hypothesis that simulated microgravity exposure, using the 6 degrees head-down tilt (HDT) bed rest model, reduces maximal forearm cutaneous vascular conductance (FVC) and sweat gland function and that exercise during HDT preserves these responses. To test these hypotheses, 20 subjects were exposed to 14 days of strict HDT bed rest. Twelve of those subjects exercised (supine cycle ergometry) at 75% of pre-bed rest heart rate maximum for 90 min/day throughout HDT bed rest. Before and after HDT bed rest, maximal FVC was measured, via plethysmography, by heating the entire forearm to 42 degrees C for 45 min. Sweat gland function was assessed by administering 1 x 10(-6) to 2 M acetylcholine (9 doses) via intradermal microdialysis while simultaneously monitoring sweat rate over the microdialysis membranes. In the nonexercise group, maximal FVC and maximal stimulated sweat rate were significantly reduced after HDT bed rest. In contrast, these responses were unchanged in the exercise group. These data suggest that 14 days of simulated microgravity exposure, using the HDT bed rest model, reduces cutaneous vasodilator and sweating capacity, whereas aerobic exercise training during HDT bed rest preserves these responses.     

Attenuated thermoregulatory sweating and cutaneous vasodilation after 14-day bed rest in humans.

We investigated the effect of head-down bed rest (HDBR) for 14 days on thermoregulatory sweating and cutaneous vasodilation in humans. Fluid intake was ad libitum during HDBR. We induced whole body heating by increasing skin temperature for 1 h with a water-perfused blanket through which hot water (42 degrees C) was circulated. The experimental room was air-conditioned (27 degrees C, 30-40% relative humidity). We measured skin blood flow (chest and forearm), skin temperatures (chest, upper arm, forearm, thigh, and calf), and tympanic temperature. We also measured sweat rate by the ventilated capsule method in which the skin area for measurement was drained by dry air conditioned at 27 degrees C under similar skin temperatures in both trials. We calculated cutaneous vascular conductance (CVC) from the ratio of skin blood flow to mean blood pressure. From tympanic temperature-sweat rate and -CVC relationships, we assessed the threshold temperature and sensitivity as the slope response of variables to a given change in tympanic temperature. HDBR increased the threshold temperature for sweating by 0.31 degrees C at the chest and 0.32 degrees C at the forearm, whereas it reduced sensitivity by 40% at the chest and 31% at the forearm. HDBR increased the threshold temperature for cutaneous vasodilation, whereas it decreased sensitivity. HDBR reduced plasma volume by 11%, whereas it did not change plasma osmolarity. The increase in the threshold temperature for sweating correlated with that for cutaneous vasodilation. In conclusion, HDBR attenuated thermoregulatory sweating and cutaneous vasodilation by increasing the threshold temperature and decreasing sensitivity. HDBR increased the threshold temperature for sweating and cutaneous vasodilation by similar magnitudes, whereas it decreased their sensitivity by different magnitudes.     

Cerebral leucine uptake and protein synthesis in the near-term ovine fetus: relation to fetal behavioral state

To investigate quantitatively how sweating and cutaneous blood flow responses at the onset of dynamic exercise are affected by increasing exercise intensity in mildly heated humans, 18 healthy male subjects performed cycle exercise at 30, 50, and 70% of maximal O2 uptake (VO2 max) for 60 s in a warm environment. The study was conducted in a climatic chamber with a regulated ambient temperature of 35 degrees C and relative humidity of 50%. The subjects rested in the semisupine position in the chamber for 60 min, and then sweating rate (SR) and skin blood flow were measured during cycle exercise at three different intensities. Changes in the heart rate, rating of perceived exertion, and mean arterial blood pressure were proportional to increasing exercise intensity, whereas esophageal and mean skin temperatures were essentially constant throughout the experiment. The SR on the chest, forearm, and thigh, but not on the palm, increased significantly with increasing exercise intensity (P < 0.05). The mean SR of the chest, forearm, and thigh increased 0.05 mg.cm-2.min-1 with an increase in exercise intensity equivalent to 10% VO2 max. On the other hand, the cutaneous vascular conductance (CVC) on the chest, forearm, and palm decreased significantly with increasing exercise intensity (P < 0.05). The mean CVC of the chest and forearm decreased 5.5% and the CVC on the palm decreased 8.0% with an increase in exercise intensity equivalent to 10% VO2 max. In addition, the reduction in CVC was greater on the palm than on the chest and forearm at all exercise intensities (P < 0.01). We conclude that nonthermal sweating and cutaneous blood flow responses are exercise intensity dependent but directionally opposite at the onset of dynamic exercise in mildly heated humans. Furthermore, cutaneous blood flow responses to increased exercise intensity are greater in glabrous (palm) than in nonglabrous (chest and forearm) skin.     

Portal vein cross-sectional area and flow and orthostatic tolerance: a 90-day bed rest study.

The objective of this study was to evaluate the changes in the portal vein cross-sectional area (PV CSA) and flow during a stand test associated with orthostatic intolerance. Eighteen subjects underwent a 90-day head-down tilt (HDT) bed rest at 6 degrees: 9 controls (Con) and 9 with flywheel exercise countermeasures (CM). At post-HDT, nine subjects (5 CM, 4 Con) were tolerant, and nine were intolerant. The PV CSA was measured by echography. We found that at HDT day 85, the PV CSA at rest had increased less in the CM subjects than in the Con (+12 vs. +27% from pre-HDT supine; P < 0.05), whereas it increased similarly in tolerant and intolerant subjects (23 and 16%, respectively). Two days after the HDT, there was a decrease in the PV CSA supine compared with the pre-HDT PV CSA supine that was similar for all groups (Con: -11%, CM: -21%; tolerant: -10%, intolerant: -16%; P < 0.05). The PV CSA decreased significantly less from supine to standing in the Con than in the CM group (-2 vs. -10% compared with the pre-HDT stand test; P < 0.05). The PV CSA also decreased significantly from supine to standing compared with the pre-HDT stand test in the tolerant group but not in the intolerant group (-20 vs. +2%; P < 0.05). From these findings, we conclude the following. 1) Because the portal vein is the only output from the splanchnic vascular area, we suggest that the lower reduction in the PV CSA and flow associated with orthostatic intolerance was related to a lower splanchnic arterial vasoconstriction. 2) The flywheel exercise CM helped to reduce the distention of the splanchnic network at rest and to maintain partially the splanchnic vasoconstriction, but it did not reduce the orthostatic intolerance.     

Cutaneous vascular responses to isometric handgrip exercise

Cutaneous vascular responses to dynamic exercise have been well characterized, but it is not known whether that response pattern applies to isometric handgrip exercise. We examined cutaneous vascular responses to isometric handgrip and dynamic leg exercise in five supine men. Skin blood flow was measured by laser-Doppler velocimetry and expressed as laser-Doppler flow (LDF). Arterial blood pressure was measured noninvasively once each minute. Cutaneous vascular conductance (CVC) was calculated as LDF/mean arterial pressure. LDF and CVC responses were measured at the forearm and chest during two 3-min periods of isometric handgrip at 30% of maximum voluntary contraction and expressed as percent changes from the preexercise levels. The skin was normothermic (32 degrees C) for the first period of handgrip and was locally warmed to 39 degrees C for the second handgrip. Finally, responses were observed during 5 min of dynamic two-leg bicycle exercise (150-175 W) at a local skin temperature of 39 degrees C. Arm LDF increased 24.5 +/- 18.9% during isometric handgrip in normothermia and 64.8 +/- 14.1% during isometric handgrip at 39 degrees C (P less than 0.05). Arm CVC did not significantly change at 32 degrees C but significantly increased 18.1 +/- 6.5% during isometric handgrip at 39 degrees C (P less than 0.05). Arm LDF decreased 12.2 +/- 7.9% during dynamic exercise at 39 degrees C, whereas arm CVC fell by 35.3 +/- 4.6% (in each case P less than 0.05). Chest LDF and CVC showed similar responses.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of muscle metaboreceptor stimulation on cutaneous blood flow from glabrous and nonglabrous skin in mildly heated humans.

Given differences in sympathetic innervation to glabrous and nonglabrous skin, we tested the hypothesis that muscle metaboreceptor regulation of cutaneous vascular conductance (CVC) differs between these skin regions. Subjects (n = 21) performed isometric handgrip exercise (IHG; 50% maximal voluntary contraction for 60 s), followed by 2 min of postexercise ischemia. Throughout IHG and postexercise ischemia, CVC was measured from glabrous (palm) and nonglabrous (forearm and chest) regions contralateral to the exercising arm. These procedures were conducted after the subjects had been exposed to an ambient temperature of 35 degrees C and a relative humidity of 50% for 60 min. These thermal conditions were intended to cause slight increases in cutaneous blood flow via sympathetic withdrawal. Esophageal, sublingual, and mean skin temperatures did not change markedly during IHG or postexercise ischemia. During IHG, forearm CVC did not change, chest CVC increased slightly, and palm CVC decreased substantially (from 100 to 34.8 +/- 3.5%; P = 0.001). During muscle metaboreceptor stimulation due to postexercise ischemia, CVC from nonglabrous regions returned to preexercise baselines, whereas CVC at the palm remained below preexercise baseline (68.2 +/- 4.2%; P = 0.001 relative to preexercise baseline). These results indicate that in mildly heated humans muscle metaboreflex stimulation is capable of modulating CVC in glabrous, but not in nonglabrous, skin.     

Regional hemodynamics during postexercise hypotension. II. Cutaneous circulation.

After an acute bout of exercise, there is an unexplained elevation in systemic vascular conductance that is not completely offset by an increase in cardiac output, resulting in a postexercise hypotension. The contributions of the splanchnic and renal circulations are examined in a companion paper (Pricher MP, Holowatz LA, Williams JT, Lockwood JM, and Halliwill JR. J Appl Physiol 97: 2065-2070, 2004). The purpose of this study was to determine the contribution of the cutaneous circulation in postexercise hypotension under thermoneutral conditions (approximately 23 degrees C). Arterial blood pressure was measured via an automated sphygmomanometer, internal temperature was measured via an ingestible pill, and skin temperature was measured with eight thermocouples. Red blood cell flux (laser-Doppler flowmetry) was monitored at four skin sites (chest, forearm, thigh, and leg), and cutaneous vascular conductance (CVC) was calculated (red blood cell flux/mean arterial pressure) and scaled as percent maximal CVC (local heating to 43 degrees C). Ten subjects [6 men and 4 women; age 23 +/- 1 yr; peak O(2) uptake (Vo(2 peak)) 45.8 +/- 2.0 ml.kg(-1).min(-1)] volunteered for this study. After supine rest (30 min), subjects exercised on a bicycle ergometer for 1 h at 60% of their Vo(2 peak) and were then positioned supine for 90 min. Exercise elicited a postexercise hypotension reaching a nadir at 46.0 +/- 4.5 min postexercise (77 +/- 1 vs. 82 +/- 2 mmHg preexercise; P < 0.05). Internal temperature increased (38.0 +/- 0.1 vs. 36.7 +/- 0.1 degrees C preexercise; P < 0.05), remaining elevated at 90 min postexercise (36.9 +/- 0.1 degrees C vs. preexercise; P < 0.05). CVC at all four skin sites was elevated by the exercise bout (P < 0.05), returning to preexercise values within 50 min postexercise (P > 0.05). Therefore, although transient changes in CVC occur postexercise, they do not appear to play an obligatory role in mediating postexercise hypotension under thermoneutral conditions.     

Cutaneous blood flow and sweat rate responses to exogenous administration of acetylcholine and methacholine.

The aim of this study was to evaluate cutaneous vasodilation and sweating responses to exogenous administration of acetylcholine (ACh) and methacholine (MCh), which have different sensitivities to endogenous cholinesterase. Four intradermal microdialysis probes were placed in dorsal forearm skin: two sites were perfused with ACh (1 x 10(-7)-1 M) and the other two with the same molar concentrations of MCh. Sweat rate (SR) and cutaneous blood flow were simultaneously assessed directly over each microdialysis membrane. Dose-response curves were constructed, and the effective concentration of the drug resulting in 50% of the maximal response (EC(50)) was identified. For SR and cutaneous vascular conductance (CVC), there were no significant differences in EC(50) between sites receiving the same drug: -1.52 +/- 0.18 and -1.19 +/- 0.09 log-molar concentration of ACh at distal and proximal sites, respectively, and -2.35 +/- 0.24 and -2.42 +/- 0.23 log-molar concentration of MCh at distal and proximal sites, respectively, for SR (P > 0.05) and -3.87 +/- 0.32 and -3.97 +/- 0.27 log-molar concentration of ACh at distal and proximal sites, respectively, and -4.78 +/- 0.17 and -4.46 +/- 0.16 log-molar concentration of MCh at distal and proximal sites, respectively, for CVC (P > 0.05). However, the EC(50) for CVC and SR was significantly lower at the MCh than at the ACh sites. A second procedure was performed to confirm that differences in responses between ACh and MCh could be attributed to different cholinesterase sensitivities. Similarly, four microdialysis membranes were placed in dorsal forearm skin: two sites were perfused with ACh and other two with MCh. However, one of each of the ACh and MCh sites was also perfused with 10 microM neostigmine (an acetylcholinesterase inhibitor). Neostigmine at the ACh site induced a leftward shift (i.e., lower EC(50)) of the SR and CVC dose-response curves compared with the site treated with ACh alone, resulting in no difference in the EC(50) for SR and CVC between the ACh + neostigmine and the MCh site. These results suggest that elevations in SR and CVC occur earlier with MCh than with ACh treatment because of differences in cholinesterase susceptibility between these drugs.     

Cold-induced cutaneous vasoconstriction is mediated by Rho kinase in vivo in human skin

Cutaneous vasoconstriction (VC) is the initial thermoregulatory response to cold exposure and can be elicited through either whole body or localized skin cooling. However, the mechanisms governing local cold-induced VC are not well understood. We tested the hypothesis that Rho kinase participates in local cold-induced cutaneous VC. In seven men and women (20-27 yr of age), up to four ventral forearm skin sites were instrumented with intradermal microdialysis fibers for localized drug delivery during cooling. Skin blood flow was monitored at each site with laser-Doppler flowmetry while local skin temperature was decreased and maintained at 24 degrees C for 40 min. Cutaneous vascular conductance (CVC; laser-Doppler flowmetry/mean arterial pressure) was expressed as percent change from 34 degrees C baseline. During the first 5 min of cooling, CVC decreased at control sites (lactated Ringer solution) to -45 +/- 6% (P < 0.001), increased at adrenoceptor-antagonized sites (yohimbine + propranolol) to 15 +/- 14% (P = 0.002), and remained unchanged at both Rho kinase-inhibited (fasudil) and adrenoceptor-antagonized + Rho kinase-inhibited sites (yohimbine + propranolol + fasudil) (-9 +/- 1%, P = 0.4 and -6 +/- 2%, P = 0.4, respectively). During the last 5 min of cooling, CVC further decreased at all sites when compared with baseline values (control, -77 +/- 4%, P < 0.001; adrenoceptor antagonized, -61 +/- 3%, P < 0.001; Rho kinase inhibited, -34 +/- 7%, P < 0.001; and adrenoceptor antagonized + Rho kinase inhibited sites, -35 +/- 3%, P < 0.001). Rho kinase-inhibited and combined treatment sites were significantly attenuated when compared with both adrenoceptor-antagonized (P < 0.01) and control sites (P < 0.0001). Rho kinase mediates both early- and late-phase cold-induced VC, supporting in vitro findings and providing a putative mechanism through which both adrenergic and nonadrenergic cold-induced VC occurs in an in vivo human thermoregulatory model.     

Body temperature and skin blood flow during a 14-day bed-rest in a head-down tilt position in humans

Exposure to microgravity or simulated microgravity is known to affect regulatory function in autonomic nervous system. With regard to thermoregulation, simulated microgravity impairs sweating and induces lower skin and higher internal temperatures during physical work. During supine rest after HDT bed rest, the internal temperatures were reported to be higher than those of pre-HDT bed rest in some studies but not in others. There is no report about the dynamic changes of skin blood flow during 14-day HDT bed rest. The process of HDT bed-rest deconditioning on the function of the thermoregulatory system is virtually unknown. The HDT induces an immediate cephalad fluid shift which would inhibit the sympathetic outflow through the arterial and cardiopulmonary baroreflexes, which may increase the skin blood flow. On the other hand, prolonged HDT bed rest induces dehydration, which will increase sympathetic outflow through cardiopulmonary baroreceptor modulation. Both sympathetic activation and dehydration itself will decrease skin blood flow. It seems probable that the general effect on skin blood flow may reverse along the HDT bed rest. However, the dynamic characters of skin blood flow and body temperature during the HDT bed rest have not been studied thoroughly. Therefore, the purpose of present study was to investigate the changes of skin blood flow and body temperature during 14 days HDT bed rest.     

Reflex control of cutaneous vasoconstrictor system is reset by exogenous female reproductive hormones.

To determine whether cardiovascular influences of exogenous female steroid hormones include effects on reflex thermoregulatory control of the adrenergic cutaneous vasoconstrictor system, we conducted ramp decreases in skin temperature (T(sk)) in eight women in both high- and low (placebo)-progesterone/estrogen phases of oral contraceptive use. With the use of water-perfused suits, T(sk) was held at 36 degrees C for 10 min (to minimize initial vasoconstrictor activity) and was then decreased in a ramp, approximately 0.2 degrees C/min for 12-15 min. Subjects rested supine for 30-40 min before each experiment, and the protocol was terminated before the onset of shivering. Skin blood flow was monitored by laser-Doppler flowmetry and arterial pressure by finger photoplethysmography. In all experiments, cutaneous vasoconstriction began immediately with the onset of cooling, and cutaneous vascular conductance (CVC) decreased progressively with decreasing T(sk). Regression analysis of the relationship of CVC to T(sk) showed no difference in slope between phases (low-hormone phase: 17.67 +/- 5.57; high-hormone phase: 17.40 +/- 8.00 %baseline/ degrees C; P > 0.05). Additional studies involving local blockade confirmed this response as being solely due to the adrenergic vasoconstrictor system. Waking oral temperature (T(or)) was significantly higher on high-hormone vs. low-hormone days (36.60 +/- 0.11 vs. 36.37 +/- 0.09 degrees C, respectively; P < 0.02). Integrative analysis of CVC in terms of simultaneous values for T(sk) and T(or) showed that the cutaneous vasoconstrictor response was shifted in the high-hormone phase such that a higher T(or) was maintained throughout cooling (P < 0.05). Thus reflex thermoregulatory control of the cutaneous vasoconstrictor system is shifted to higher internal temperatures by exogenous female reproductive hormones.     

Influence of female reproductive hormones on local thermal control of skin blood flow.

Progesterone and estrogen modify thermoregulatory control such that, when both steroids are elevated, body temperature increases and the reflex thermoregulatory control of cutaneous vasodilation is shifted to higher internal temperatures. We hypothesized that the influence of these hormones would also include effects on local thermal control of skin blood flow. Experiments were conducted in women in high-hormone (HH) and low-hormone (LH) phases of oral contraceptive use. Skin blood flow was measured by laser-Doppler flowmetry, and local temperature (T(loc)) was controlled over 12 cm(2) around the sites of blood flow measurement. T(loc) was held at 32 degrees C for 10-15 min and was then decreased at one site from 32 to 20 degrees C in a ramp over 20 min. Next, T(loc) was increased from 32 to 42 degrees C in a ramp over 15 min at a separate site. Finally, T(loc) at both sites was held at 42 degrees C for 30 min to elicit maximum vasodilation; data for cutaneous vascular conductance (CVC) are expressed relative to that maximum. Whole body skin temperature (T(sk)) was held at 34 degrees C throughout each study to minimize reflex effects from differences in T(sk) between experiments. Baseline CVC did not differ between phases [8.18 +/- 1.38 (LH) vs. 8. 41 +/- 1.31% of maximum (HH); P > 0.05]. The vasodilator response to local warming was augmented in HH (P < 0.05, ANOVA). For example, at T(loc) of 40-42 degrees C, CVC averaged 76.41 +/- 3.08% of maximum in HH and 67.71 +/- 4.43% of maximum in LH (P < 0.01 LH vs. HH). The vasoconstrictor response to local cooling was unaffected by phase (P > 0.05). These findings indicate that modifications in cutaneous vascular control by female steroid hormones include enhancement of the vasodilator response to local warming and are consistent with reports of the influence of estrogen to enhance nitric oxide-dependent vasodilator responses.     

Heat acclimation increases skin vasodilation and sweating but not cardiac baroreflex responses in heat-stressed humans.

In the present study, to test the hypothesis that exercise-heat acclimation increases orthostatic tolerance via the improvement of cardiac baroreflex control in heated humans, we examined cardiac baroreflex and thermoregulatory responses, including cutaneous vasomotor and sudomotor responses, during whole body heating before and after a 6-day exercise-heat acclimation program [4 bouts of 20-min exercise at 50% peak rate of oxygen uptake separated by 10-min rest in the heat (36 degrees C; 50% relative humidity)]. Ten healthy young volunteers participated in the study. On the test days before and after the heat acclimation program, subjects underwent whole body heat stress produced by a hot water-perfused suit during supine rest for 45 min and 75 degrees head-up tilt (HUT) for 6 min. The sensitivity of the arterial baroreflex control of heart rate (HR) was calculated from the spontaneous changes in beat-to-beat arterial pressure and HR. The HUT induced a presyncopal sign in seven subjects in the preacclimation test and in six subjects in the postacclimation test, and the tilting time did not differ significantly between the pre- (241 +/- 33 s) and postacclimation (283 +/- 24 s) tests. Heat acclimation did not change the slope in the HR-esophageal temperature (Tes) relation and the cardiac baroreflex sensitivity during heating. Heat acclimation decreased (P < 0.05) the Tes thresholds for cutaneous vasodilation in the forearm and dorsal hand and for sweating in the forearm and chest. These findings suggest that short-term heat acclimation does not alter the spontaneous baroreflex control of HR during heat stress, although it induces adaptive change of the heat dissipation response in nonglabrous skin.     

Evidence of a myogenic response in vasomotor control of forearm and palm cutaneous microcirculations.

Previous investigations of autoregulatory mechanisms in the control of skin blood flow suffer from the possibility of interfering effects of the autonomic nervous system. To address this question, in 11 subjects cutaneous vascular responses were measured during acute changes in perfusion pressure (using Valsalva maneuver; VM) before and after ganglionic blockade via systemic trimethaphan infusion. Cutaneous vascular conductance at baseline (CVC(base)) and during the last 5 s of the VM (CVC(VM)) were measured from forearm (nonglabrous) and palm (glabrous) skin. During the VM without ganglionic blockade, compared with CVC(base), CVC(VM) decreased significantly at the palm [0.79 +/- 0.17 to 0.55 +/- 0.17 arbitrary units (AU)/mmHg; P = 0.002] but was unchanged at the forearm (0.13 +/- 0.02 to 0.16 +/- 0.02 AU/mmHg; P = 0.50). After ganglionic blockade, VM induced pronounced decreases in perfusion pressure, which resulted in significant increases in CVC(VM) at both forearm (0.19 +/- 0.03 to 0.31 +/- 0.07 AU/mmHg; P = 0.008) and palm (1.84 +/- 0.29 to 2.76 +/- 0.63 AU/mmHg; P = 0.003) sites. These results suggest that, devoid of autonomic control, both glabrous and nonglabrous skin are capable of exhibiting vasomotor autoregulation during pronounced reductions in perfusion pressure.     

Reflex control of the cutaneous circulation after acute and chronic local capsaicin.

To investigate whether local activity of capsaicin-sensitive sensory afferents in the skin has a modulatory role in the reflex cutaneous vasodilator response to hyperthermia in humans, experiments were conducted in two parts. First, low-dose topical capsaicin (0.025%) was administered acutely to stimulate local activity of these afferents. Second, we temporarily desensitized these nerves in a small area of skin using chronic capsaicin treatment (0.075% for 7 days). Each intervention was followed by whole body heating using water-perfused suits and then by local warming to 42 degrees C for assessment of maximum cutaneous vascular conductance. Skin blood flow was measured by laser-Doppler flowmetry and divided by mean arterial pressure (Finapres) for assessment of cutaneous vascular conductance. Maximum vascular conductance was not influenced by either acute or chronic capsaicin treatment (P > 0.10). After acute capsaicin, baseline cutaneous vascular conductance was elevated above that at control sites (25.34 +/- 6.25 vs. 10.57 +/- 2.42%max; P < 0.05). However, internal temperature thresholds for vasodilation were not affected by either acute or chronic capsaicin (P > 0.10). Furthermore, neither acute (control: 112.74 +/- 36.83 vs. acute capsaicin: 96.92 +/- 28.92%max/ degrees C; P > 0.10) nor chronic (control: 142.45 +/- 61.89 vs. chronic capsaicin: 132.12 +/- 52.60%max/ degrees C; P > 0.10) capsaicin administration influenced the sensitivity of the reflex cutaneous vasodilator response. We conclude that local activity of capsaicin-sensitive afferents in the skin does not modify reflex cutaneous vasodilation during hyperthermia.     

Does local heating-induced nitric oxide production attenuate vasoconstrictor responsiveness to lower body negative pressure in human skin?

We tested the hypothesis that local heating-induced nitric oxide (NO) production attenuates cutaneous vasoconstrictor responsiveness. Eleven subjects (6 men, 5 women) had four microdialysis membranes placed in forearm skin. Two membranes were perfused with 10 mM of N(G)-nitro-L-arginine (L-NAME) and two with Ringer solution (control), and all sites were locally heated to 34 degrees C. Subjects then underwent 5 min of 60-mmHg lower body negative pressure (LBNP). Two sites (a control and an L-NAME site) were then heated to 39 degrees C, while the other two sites were heated to 42 degrees C. At the L-NAME sites, skin blood flow was elevated using 0.75-2 mg/ml of adenosine in the perfusate solution (Adn + L-NAME) to a similar level relative to control sites. Subjects then underwent another 5 min of 60-mmHg LBNP. At 34 degrees C, cutaneous vascular conductance (CVC) decreased (Delta) similarly at both control and L-NAME sites during LBNP (Delta7.9 +/- 3.0 and Delta3.4 +/- 0.8% maximum, respectively; P > 0.05). The reduction in CVC to LBNP was also similar between control and Adn + L-NAME sites at 39 degrees C (control Delta11.4 +/- 2.5 vs. Adn + L-NAME Delta7.9 +/- 2.0% maximum; P > 0.05) and 42 degrees C (control Delta1.9 +/- 2.7 vs. Adn + L-NAME Delta 4.2 +/- 2.7% maximum; P > 0.05). However, the decrease in CVC at 42 degrees C, regardless of site, was smaller than at 39 degrees C (P < 0.05). These results do not support the hypothesis that local heating-induced NO production attenuates cutaneous vasoconstrictor responsiveness during high levels of LBNP. However, elevated local temperature, per se, attenuates cutaneous vasoconstrictor responsiveness to LBNP, presumably through non-nitric oxide mechanisms.     

Transcapillary fluid shifts in tissues of the head and neck during and after simulated microgravity.

To understand the mechanism, magnitude, and time course of facial puffiness that occurs in microgravity, seven male subjects were tilted 6 degrees head-down for 8 h, and all four Starling transcapillary pressures were directly measured before, during, and after tilt. Head-down tilt (HDT) caused facial edema and a significant elevation of microvascular pressures measured in the lower lip: capillary pressures increased from 27.7 +/- 1.5 mmHg (mean +/- SE) pre-HDT to 33.9 +/- 1.7 mmHg by the end of tilt. Subcutaneous and intramuscular interstitial fluid pressures in the neck also increased as a result of HDT, whereas interstitial fluid colloid osmotic pressures remained unchanged. Plasma colloid osmotic pressure dropped significantly by 4 h of HDT (21.5 +/- 1.5 mmHg pre-HDT to 18.2 +/- 1.9 mmHg), suggesting a transition from fluid filtration to absorption in capillary beds between the heart and feet during HDT. After 4 h of seated recovery from HDT, microvascular pressures in the lip (capillary and venule pressures) remained significantly elevated by 5-8 mmHg above baseline values. During HDT, urine output was 126.5 ml/h compared with 46.7 ml/h during the control baseline period. These results suggest that facial edema resulting from HDT is caused primarily by elevated capillary pressures and decreased plasma colloid osmotic pressures. The negativity of interstitial fluid pressures above heart level also has implications for maintenance of tissue fluid balance in upright posture.