VASOMOTOR RESPONSES OF ISOLATED PERIPHERAL BLOOD VESSELS FROM BOWHEAD WHALES: THERMOREGULATORY IMPLICATIONS

Temperature regulation in bowhead whales, Balaena mysticetus , is supported by the characteristic cetacean peripheral circulation, especially notable in the tail flukes. Blood vessels serving this function consist of countercurrent heat exchangers (network of veins surrounding a central artery) favoring heat conservation and an alternate routing via arteriovenous anastomoses (AVAs) providing for heat dissipation. We tested the vasomotor responses of isolated segments of countercurrent arteries and AVAs from the bowhead tail flukes to norepinephrine (NOR), the sympathetic adrenergic neurotransmitter. Isometric tension developed during exposure to a micromolar concentration of NOR was consistently higher in AVAs than in arteries. Accordingly, the AVAs are subject to sympathetic vasoconstriction, and this activation directs blood flow to countercurrent heat exchangers and results in heat conservation. In contrast, AVA relaxation by reduced sympathetic activation favors increased blood flow through AVAs and consequent peripheral heat loss.     

Cutaneous vascular responses to isometric handgrip exercise during local heating and hyperthermia.

The dramatic increase in skin blood flow and sweating observed during heat stress is mediated by poorly understood sympathetic cholinergic mechanisms. One theory suggests that a single sympathetic cholinergic nerve mediates cutaneous active vasodilation (AVD) and sweating via cotransmission of separate neurotransmitters, because AVD and sweating track temporally and directionally when activated during passive whole body heat stress. It has also been suggested that these responses are regulated independently, because cutaneous vascular conductance (CVC) has been shown to decrease, whereas sweat rate increases, during combined hyperthermia and isometric handgrip exercise. We tested the hypothesis that CVC decreases during isometric handgrip exercise if skin blood flow is elevated using local heating to levels similar to that induced by pronounced hyperthermia but that this does not occur at lower levels of skin blood flow. Subjects performed isometric handgrip exercise as CVC was elevated at selected sites to varying levels by local heating (which is independent of AVD) in thermoneutral and hyperthermic conditions. During thermoneutral isometric handgrip exercise, CVC decreased at sites in which blood flow was significantly elevated before exercise (-6.5 +/- 1.8% of maximal CVC at 41 degrees C and -10.5 +/- 2.0% of maximal CVC at 43 degrees C; P < 0.05 vs. preexercise). During isometric handgrip exercise in the hyperthermic condition, an observed decrease in CVC was associated with the level of CVC before exercise. Taken together, these findings argue against withdrawal of AVD to explain the decrease in CVC observed during isometric handgrip exercise in hyperthermic conditions.     

Influence of isometric exercise on blood flow and sweating in glabrous and nonglabrous human skin.

The distribution of the reflex effects of isometric exercise on cutaneous vasomotor and sudomotor function is not clear. We examined the effects of isometric exercise by different muscle masses on skin blood flow (SkBF) and sweat rate (SR) in nonglabrous skin and in glabrous skin. The latter contains arteriovenous anastomoses (AVAs), which cause large fluctuations in SkBF. SkBF was measured by laser-Doppler flowmetry (LDF) and reported as cutaneous vascular conductance (CVC; LDF/mean arterial pressure). SR was measured by capacitance hygrometry. LDF and SR were measured at the sole, palm, forearm, and ventral leg during separate bouts of isometric handgrip (IHG) and isometric leg extension (ILE). CVC and its standard deviation decreased significantly during IHG and ILE in the palm and sole (P < 0.05) but not in the forearm or leg (P > 0.05). Only palmar SR increased significantly during IHG and ILE (P < 0.05). We conclude that the major reflex influences of isometric exercise on the skin include AVAs and palmar sweat glands and that this is true for both arm and leg exercise.     

Cholinergic mechanisms of cutaneous active vasodilation during heat stress in cystic fibrosis.

To test the hypothesis that cutaneous active vasodilation in heat stress is mediated by a redundant cholinergic cotransmitter system, we examined the effects of atropine on skin blood flow (SkBF) increases during heat stress in persons with (CF) and without cystic fibrosis (non-CF). Vasoactive intestinal peptide (VIP) has been implicated as a mediator of cutaneous vasodilation in heat stress. VIP-containing cutaneous neurons are sparse in CF, yet SkBF increases during heat stress are normal. In CF, augmented ACh release or muscarinic receptor sensitivity could compensate for decreased VIP; if so, active vasodilation would be attenuated by atropine in CF relative to non-CF. Atropine was administered into skin by iontophoresis in seven CF and seven matched non-CF subjects. SkBF was monitored by laser-Doppler flowmetry (LDF) at atropine treated and untreated sites. Blood pressure [mean arterial pressure (MAP)] was monitored (Finapres), and cutaneous vascular conductance was calculated (CVC = LDF/MAP). The protocol began with a normothermic period followed by a 3-min cold stress and 30-45 min of heat stress. Finally, LDF sites were warmed to 42 degrees C to effect maximal vasodilation. CVC was normalized to its site-specific maximum. During heat stress, CVC increased in both CF and non-CF (P < 0.01). CVC increases were attenuated by atropine in both groups (P < 0.01); however, the responses did not differ between groups (P = 0.99). We conclude that in CF there is not greater dependence on redundant cholinergic mechanisms for cutaneous active vasodilation than in non-CF.     

In vivo mechanisms of cutaneous vasodilation and vasoconstriction in humans during thermoregulatory challenges.

This review focuses on the neural and local mechanisms that have been demonstrated to effect cutaneous vasodilation and vasoconstriction in response to heat and cold stress in vivo in humans. First, our present understanding of the mechanisms by which sympathetic cholinergic nerves mediate cutaneous active vasodilation during reflex responses to whole body heating is discussed. These mechanisms include roles for cotransmission as well as nitric oxide (NO). Next, the mechanisms by which sympathetic noradrenergic nerves mediate cutaneous active vasoconstriction during whole body cooling are reviewed, including cotransmission by neuropeptide Y (NPY) acting through NPY Y1 receptors. Subsequently, current concepts for the mechanisms that effect local cutaneous vascular responses to direct skin warming are examined. These mechanisms include the roles of temperature-sensitive afferent neurons as well as NO in causing vasodilation during local heating of skin. This section is followed by a review of the mechanisms that cause local cutaneous vasoconstriction in response to direct cooling of the skin, including the dependence of these responses on intact sensory and sympathetic, noradrenergic innervation as well as roles for nonneural mechanisms. Finally, unresolved issues that warrant further research on mechanisms that control cutaneous vascular responses to heating and cooling are discussed.     

Endothelial nitric oxide synthase control mechanisms in the cutaneous vasculature of humans in vivo

Nitric oxide (NO) participates in locally mediated vasodilation induced by increased local skin temperature (T(loc)) and in sympathetically mediated vasodilation during whole body heat stress. We hypothesized that endothelial NOS (eNOS) participates in the former, but not the latter, response. We tested this hypothesis by examining the effects of the eNOS antagonist N(G)-amino-l-arginine (l-NAA) on skin blood flow (SkBF) responses to increased T(loc) and whole body heat stress. Microdialysis probes were inserted into forearm skin for drug delivery. One microdialysis site was perfused with l-NAA in Ringer solution and a second site with Ringer solution alone. SkBF [laser-Doppler flowmetry (LDF)] and blood pressure [mean arterial pressure (MAP)] were monitored, and cutaneous vascular conductance (CVC) was calculated (CVC = LDF / MAP). In protocol 1, T(loc) was controlled with LDF/local heating units. T(loc) initially was held at 34 degrees C and then increased to 41.5 degrees C. In protocol 2, after a normothermic period, whole body heat stress was induced (water-perfused suits). At the end of both protocols, 58 mM sodium nitroprusside was perfused at both microdialysis sites to cause maximal vasodilation for data normalization. In protocol 1, CVC at 34 degrees C T(loc) did not differ between l-NAA-treated and untreated sites (P > 0.05). Local skin warming to 41.5 degrees C T(loc) increased CVC at both sites. This response was attenuated at l-NAA-treated sites (P < 0.05). In protocol 2, during normothermia, CVC did not differ between l-NAA-treated and untreated sites (P > 0.05). During heat stress, CVC rose to similar levels at l-NAA-treated and untreated sites (P > 0.05). We conclude that eNOS is predominantly responsible for NO generation in skin during responses to increased T(loc), but not during reflex responses to whole body heat stress.     

Local heating, but not indirect whole body heating, increases human skeletal muscle blood flow

For decades it was believed that direct and indirect heating (the latter of which elevates blood and core temperatures without directly heating the area being evaluated) increases skin but not skeletal muscle blood flow. Recent results, however, suggest that passive heating of the leg may increase muscle blood flow. Using the technique of positron-emission tomography, the present study tested the hypothesis that both direct and indirect heating increases muscle blood flow. Calf muscle and skin blood flows were evaluated from eight subjects during normothermic baseline, during local heating of the right calf [only the right calf was exposed to the heating source (water-perfused suit)], and during indirect whole body heat stress in which the left calf was not exposed to the heating source. Local heating increased intramuscular temperature of the right calf from 33.4 ± 1.0°C to 37.4 ± 0.8°C, without changing intestinal temperature. This stimulus increased muscle blood flow from 1.4 ± 0.5 to 2.3 ± 1.2 ml·100 g?1·min?1 (P < 0.05), whereas skin blood flow under the heating source increased from 0.7 ± 0.3 to 5.5 ± 1.5 ml·100 g?1·min?1 (P < 0.01). While whole body heat stress increased intestinal temperature by ～1°C, muscle blood flow in the calf that was not directly exposed to the water-perfused suit (i.e., indirect heating) did not increase during the whole body heat stress (normothermia: 1.6 ± 0.5 ml·100 g?1·min?1; heat stress: 1.7 ± 0.3 ml·100 g?1·min?1; P = 0.87). Whole body heating, however, reflexively increased calf skin blood flow (to 4.0 ± 1.5 ml·100 g?1·min?1) in the area not exposed to the water-perfused suit. These data show that local, but not indirect, heating increases calf skeletal muscle blood flow in humans. These results have important implications toward the reconsideration of previously accepted blood flow distribution during whole body heat stress.     

Delayed threshold for active cutaneous vasodilation in patients with Type 2 diabetes mellitus.

Epidemiological evidence suggests decreased heat tolerance in patients with Type 2 diabetes mellitus (T2DM), but it is not known whether the mechanisms involved in thermoregulatory control of skin blood flow are altered in these patients. We tested the hypothesis that individuals with T2DM have a delayed internal temperature threshold for active cutaneous vasodilation during whole body heating compared with healthy control subjects. We measured skin blood flow using laser-Doppler flowmetry (LDF), internal temperature (T or) via sublingual thermocouple, and mean arterial pressure via Finometer at baseline and during whole body heating in 9 T2DM patients and 10 control subjects of similar age, height, and weight. At one LDF site, sympathetic noradrenergic neurotransmission was blocked by local pretreatment with bretylium tosylate (BT) to isolate the cutaneous active vasodilator system. Whole body heating was conducted using a water-perfused suit. There were no differences in preheating T(or) between groups (P > 0.10). Patients with T2DM exhibited an increased internal temperature threshold for the onset of vasodilation at both untreated and BT-treated sites. At BT-treated sites, T or thresholds were 36.28 +/- 0.07 degrees C in controls and 36.55 +/- 0.05 degrees C in T2DM patients (P < 0.05), indicating delayed onset of active vasodilation in patients. Sensitivity of vasodilation was variable in both groups, with no consistent difference between groups (P > 0.05). We conclude that altered control of active cutaneous vasodilation may contribute to impaired thermoregulation in patients with T2DM.     

Mode of neural control mediating rat tail vasodilation during heating

The purpose of this investigation was to delineate the mode of efferent neural control mediating rat tail vasodilation during body heating. Tail blood flow (venous occlusion plethysmography), tail skin temperature over the ventral vascular bundle, and arterial pressure were measured in Sprague-Dawley rats anesthetized with pentobarbital sodium (45 mg/kg). Three protocols were followed: anesthesia of the lumbar sympathetic chain, bilateral lumbar sympathectomy, and sympathetic nerve stimulation during varying degrees of alpha-adrenergic receptor blockade. Mean tail blood flow and tail vascular conductance (TVC) during body heating were 40.3 +/- 8.7 ml X 100 ml-1 X min-1 and 39.2 +/- 9.2 ml X 100 ml-1 X min-1 X 100 mmHg-1, respectively. Interruption of sympathetic nerve activity by sympathetic nerve anesthetization or sympathectomy during heat stress caused a nonsignificant increase in TVC to 112.7 +/- 1.8 and 121.12 +/- 6.3%, respectively, of the values achieved with body heating. Sympathectomy performed in normothermic animals that had recovered from prior heating caused an increase in TVC to 128.4 +/- 14.0% of the levels achieved during the previous heating period. In addition, sympathetic nerve stimulation after complete alpha-adrenergic receptor blockade failed to produce a vasodilation [control TVC = 10.2 +/- 3.9 vs. TVC during nerve stimulation = 10.4 +/- 3.9 (P greater than 0.05)]. It is concluded that the increase in TVC during body heating occurs solely via a reduction in vasoconstrictor nerve activity.     

Transient receptor potential vanilloid type 1 channels contribute to reflex cutaneous vasodilation in humans

Mechanisms underlying the cutaneous vasodilation in response to an increase in core temperature remain unresolved. The purpose of this study was to determine a potential contribution of transient receptor potential vanilloid type 1 (TRPV-1) channels to reflex cutaneous vasodilation. Twelve subjects were equipped with four microdialysis fibers on the ventral forearm, and each site randomly received 1) 90% propylene glycol + 10% lactated Ringer (vehicle control); 2) 10 mM l-NAME; 3) 20 mM capsazepine to inhibit TRPV-1 channels; 4) combined 10 mM l-NAME + 20 mM capsazepine. Whole body heating was achieved via water-perfused suits sufficient to raise oral temperature at least 0.8°C above baseline. Maximal skin blood flow was achieved by local heating to 43°C and infusion of 28 mM nitroprusside. Systemic arterial pressure (SAP) was measured, and skin blood flow was monitored via laser-Doppler flowmetry (LDF). Cutaneous vascular conductance (CVC) was calculated as LDF/SAP and normalized to maximal vasodilation (%CVC(max)). Capsazepine sites were significantly reduced compared with control (50 ± 4%CVC(max) vs. 67 ± 5%CVC(max), respectively; P < 0.05). l-NAME (33 ± 3%CVC(max)) and l-NAME + capsazepine (30 ± 4%CVC(max)) sites were attenuated compared with control (P < 0.01) and capsazepine (P < 0.05); however, there was no difference between l-NAME and combined l-NAME + capsazepine. These data suggest TRPV-1 channels participate in reflex cutaneous vasodilation and TRPV-1 channels may account for a portion of the NO component. TRPV-1 channels may have a direct neural contribution or have an indirect effect via increased arterial blood temperature. Whether the TRPV-1 channels directly or indirectly contribute to reflex cutaneous vasodilation remains uncertain.     

Responsiveness of microcirculation and local cold vasodilation to capsaicin in the intact and chronically denervated canine tongue

Lingual blood flow and its distribution were determined at rest and in response to local cooling of the tongue (32 degrees C) in 6 anaesthetized, paralyzed and artificially ventilated dogs before and after two intraarterial (i.a.) injections of capsaicin (2.5 mg) at an interval of about 40 min. In 3 dogs, the same protocol was performed after degeneration of the chorda-lingual and glossopharyngeal nerves due to prior transection. In general the first i.a. injection of capsaicin resulted in a marked and the second injection in a smaller decrease of lingual blood flow. Local cooling of the tongue induced significant increases in lingual blood flow before as well as after capsaicin treatment, regardless of whether sensory innervation was intact or degenerated. In both the untreated and capsaicin treated dogs the increase in lingual blood flow during local cooling of the tongue was solely due to an increase in blood flow through the arteriovenous anastomoses, while blood flow through the capillaries of the mucosa and muscles even decreased. The findings suggest that capsaicin-induced vasoconstriction of the tongue vessels is due to a direct effect on vascular receptors. It is further suggested that cold vasodilatation of the canine tongue is not mediated by axon collaterals releasing substance P. Direct thermal effects on the intramural ganglia and the postganglionic vasomotor efferents innervating the AVAs, or on AVAs basal tone itself are suggested as the underlying mechanism.     

Nitric oxide concentration increases in the cutaneous interstitial space during heat stress in humans.

To examine the role of nitric oxide (NO) in cutaneous active vasodilation, we measured the NO concentration from skin before and during whole body heat stress in nine healthy subjects. A forearm site was instrumented with a NO-selective, amperometric electrode and an adjacent intradermal microdialysis probe. Skin blood flow (SkBF) was monitored by laser-Doppler flowmetry (LDF). NO concentrations and LDF were measured in normothermia and heat stress. After heat stress, a solution of ACh was perfused through the microdialysis probe to pharmacologically generate NO and verify the electrode's function. During whole body warming, both SkBF and NO concentrations began to increase at the same internal temperature. Both SkBF and NO concentrations increased during heat stress (402 +/- 76% change from LDF baseline, P < 0.05; 22 +/- 5% change from NO baseline, P < 0.05). During a second baseline condition after heat stress, ACh perfusion led to increases in both SkBF and NO concentrations (496 +/- 119% change from LDF baseline, P < 0.05; 16 +/- 10% change from NO baseline, P < 0.05). We conclude that NO does increase in skin during heat stress in humans, attendant to active vasodilation. This result suggests that NO has a role beyond that of a permissive factor in the process; rather, NO may well be an effector of cutaneous vasodilation during heat stress.     

Bradykinin does not mediate cutaneous active vasodilation during heat stress in humans.

To test the hypothesis that bradykinin effects cutaneous active vasodilation during hyperthermia, we examined whether the increase in skin blood flow (SkBF) during heat stress was affected by blockade of bradykinin B(2) receptors with the receptor antagonist HOE-140. Two adjacent sites on the forearm were instrumented with intradermal microdialysis probes for local delivery of drugs in eight healthy subjects. HOE-140 was dissolved in Ringer solution (40 microM) and perfused at one site, whereas the second site was perfused with Ringer alone. SkBF was monitored by laser-Doppler flowmetry (LDF) at both sites. Mean arterial pressure (MAP) was monitored from a finger, and cutaneous vascular conductance (CVC) was calculated (CVC = LDF/MAP). Water-perfused suits were used to control body temperature and evoke hyperthermia. After hyperthermia, both microdialysis sites were perfused with 28 mM nitroprusside to effect maximal vasodilation. During hyperthermia, CVC increased at HOE-140 (69 +/- 2% maximal CVC, P < 0.01) and untreated sites (65 +/- 2% maximal CVC, P < 0.01). These responses did not differ between sites (P > 0.05). Because the bradykinin B(2)-receptor antagonist HOE-140 did not alter SkBF responses to heat stress, we conclude that bradykinin does not mediate cutaneous active vasodilation.     

Heat stress reduces cerebral blood velocity and markedly impairs orthostatic tolerance in humans

Orthostatic tolerance is reduced in the heat-stressed human. This study tested the following hypotheses: 1) whole body heat stress reduces cerebral blood velocity (CBV) and increases cerebral vascular resistance (CVR); and 2) reductions in CBV and increases in CVR in response to an orthostatic challenge will be greater while subjects are heat stressed. Fifteen subjects were instrumented for measurements of CBV (transcranial ultrasonography), mean arterial blood pressure (MAP), heart rate, and internal temperature. Whole body heating increased both internal temperature (36.4+/-0.1 to 37.3+/-0.1 degrees C) and heart rate (59+/-3 to 90+/-3 beats/min); P<0.001. Whole body heating also reduced CBV (62+/-3 to 53+/-2 cm/s) primarily via an elevation in CVR (1.35+/-0.06 to 1.63+/-0.07 mmHg.cm-1.s; P<0.001. A subset of subjects (n=8) were exposed to lower-body negative pressure (LBNP 10, 20, 30, 40 mmHg) in both normothermic and heat-stressed conditions. During normothermia, LBNP of 30 mmHg (highest level of LBNP achieved by the majority of subjects in both thermal conditions) did not significantly alter CBV, CVR, or MAP. During whole body heating, this LBNP decreased MAP (81+/-2 to 75+/-3 mmHg), decreased CBV (50+/-4 to 39+/-1 cm/s), and increased CVR (1.67+/-0.17 to 1.92+/-0.12 mmHg.cm-1.s); P<0.05. These data indicate that heat stress decreases CBV, and the reduction in CBV for a given orthostatic challenge is greater during heat stress. These outcomes reduce the reserve to buffer further decreases in cerebral perfusion before presyncope. Increases in CVR during whole body heating, coupled with even greater increases in CVR during orthostasis and heat stress, likely contribute to orthostatic intolerance.     

A subsidiary fever center in the medullary raphé?

In fever, as in normal thermoregulation, signals from the preoptic area drive both cutaneous vasoconstriction and thermogenesis by brown adipose tissue (BAT). Both of these responses are mediated by sympathetic nerves whose premotor neurons are located in the medullary raphé. EP3 receptors, key prostaglandin E2 (PGE2) receptors responsible for fever induction, are expressed in this same medullary raphé region. To investigate whether PGE2 in the medullary raphé might contribute to the febrile response, we tested whether direct injections of PGE2 into the medullary raphé could drive sympathetic nerve activity (SNA) to BAT and cutaneous (tail) vessels in anesthetized rats. Microinjections of glutamate (50 mM, 60-180 nl) into the medullary raphé activated both tail and BAT SNA, as did cooling the trunk skin. PGE2 injections (150-500 ng in 300-1,000 nl) into the medullary raphé had no effect on tail SNA, BAT SNA, body temperature, or heart rate. By contrast, 150 ng PGE2 injected into the preoptic area caused large increases in both tail and BAT SNA (+60 +/- 17 spikes/15 s and 1,591 +/- 150% of control, respectively), increased body temperature (+1.8 +/- 0.2 degrees C), blood pressure (+17 +/- 2 mmHg), and heart rate (+124 +/- 19 beats/min). These results suggest that despite expression of EP3 receptors, neurons in the medullary raphé are unable to drive febrile responses of tail and BAT SNA independently of the preoptic area. Rather, they appear merely to transmit signals for heat production and heat conservation originating from the preoptic area.     

The neurogenic constrictor response of isolated rat saphenous artery is reduced after 2-week tail suspension

Under real or simulated microgravity conditions the control of arterial vascular tone is greatly disturbed. The low arterial vessel reactivity to sympathetic influences may be the cause of an increase in flow in hind limb skeletal muscles in tail-suspended (TS) rats. Our previous experiments with constant pressure perfusion of rat hind limb demonstrated the reduced vasoconstrictor responses to sympathetic nerve stimulation in TS rats. Responses to exogenous noradrenaline depended on the perfusion conditions. It is known that the vessels of various branching orders noticeably differ in nerve density and in sensitivity to vasoconstrictor agonists. So under neurogenic or exogenous noradrenaline influences the vascular resistance may be increased at different levels of vascular bed, thus making the data analysis seriously complicated. This uncertainty may be overcome by investigation of a single vessel isolated from hind limb vascular bed. The saphenous artery, a resistance artery with dense innervation, is a very convenient object for this purpose. Thus, this study was aimed at comparing the effects of 2-week tail suspension upon the constrictor responses of isolated saphenous artery to neurogenic and exogenous noradrenaline stimuli in rats.     

Cutaneous interstitial nitric oxide concentration does not increase during heat stress in humans.

Inhibition of cutaneous nitric oxide (NO) synthase reduces the magnitude of cutaneous vasodilation during whole body heating in humans. However, this observation is insufficient to conclude that NO concentration increases in the skin during a heat stress. This study was designed to test the hypothesis that whole body heating increases cutaneous interstitial NO concentration. This was accomplished by placing 2 microdialysis membranes in the forearm dermal space of 12 subjects. Both membranes were perfused with lactated Ringer solutions at a rate of 2 microl/min. In both normothermia and during whole body heating via a water perfused suit, dialysate from these membranes were obtained and analyzed for NO using the chemiluminescence technique. In six of these subjects, after the heat stress, the membranes were perfused with a 1 M solution of acetylcholine to stimulate NO release. Dialysate from these trials was also assayed to quantify cutaneous interstitial NO concentration. Whole body heating increased skin temperature from 34.6 +/- 0.2 to 38.8 +/- 0.2 degrees C (P < 0.05), which increased sublingual temperature (36.4 +/- 0.1 to 37.6 +/- 0.1 degrees C; P < 0.05), heart rate (63 +/- 5 to 93 +/- 5 beats/min; P < 0.05), and skin blood flow over the membranes (21 +/- 4 to 88 +/- 10 perfusion units; P < 0.05). NO concentration in the dialysate did not increase significantly during of the heat stress (7.6 +/- 0.7 to 8.6 +/- 0.8 microM; P > 0.05). After the heat stress, administration of acetylcholine in the perfusate significantly increased skin blood flow (128 +/- 6 perfusion units) relative to both normothermic and heat stress values and significantly increased NO concentration in the dialysate (15.8 +/- 2.4 microM). These data suggest that whole body heating does not increase cutaneous interstitial NO concentration in forearm skin. Rather, NO may serve in a permissive role in facilitating the effects of an unknown neurotransmitter, leading to cutaneous vasodilation during a heat stress.     

Dynamic evaluation of blood flow microcirculation by combined use of the laser Doppler flowmetry and high‐speed videocapillaroscopy methods

The dynamic light scattering methods are widely used in biomedical diagnostics involving evaluation of blood flow. However, there exist some difficulties in quantitative interpretation of backscattered light signals from the viewpoint of diagnostic information. This study considers the application of the high‐speed videocapillaroscopy (VCS) method that provides the direct measurement of the red blood cells (RBCs) velocity into a capillary. The VCS signal presents true oscillation nature of backscattered light caused by moving RBCs. Thus, the VCS signal can be assigned as a reference one with respect to more complicated signals like in laser Doppler flowmetry (LDF). An essential correlation between blood flow velocity oscillations in a separate human capillary and the integral perfusion estimate obtained by the LDF method has been found. The observation of blood flow by the VCS method during upper arm occlusion has shown emergence of the reverse blood flow effect in capillaries that corresponds to the biological zero signal in the LDF. The reverse blood flow effect has to be taken into account in interpretation of LDF signals.      

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)     

Adrenoceptor and local modulator control of cutaneous blood flow in thermal stress

Blood flow to the skin is controlled by body temperatures in two ways: core and mean skin temperature combine in the central nervous system to form a reflex mechanism that controls the frequency of activity in sympathetic nerves to the cutaneous blood vessels; and local mechanisms independent of reflex effects control contractile response to the sympathetic transmitter norepinephrine (NE) at different temperatures. Cutaneous vessels differ in responsiveness to NE across temperatures: in limbs and tails, the superficial vessels constrict more strongly to NE when cooled, while the deep vessels show weaker responses to NE when cooled. This allows the limb to dissipate heat when warm and to conserve heat when cool. The mechanism for this difference in thermal response of deep and superficial vessels is not completely known, but may relate to differences in the adrenoceptors on which NE acts, and/or to the actions of locally produced substances that modulate the responses to NE in different ways at different temperatures. This paper discusses the alpha1- and alpha2-adrenoceptors involved in contraction of deep and superficial cutaneous vessels and also describes the roles of the local modulator nitric oxide, which interacts with adrenoceptors to affect cutaneous blood flow.