Hindlimb vascular responses to sympathetic augmentation during acute anemia

The effect of increased sympathetic activity on skeletal muscle blood flow during acute anemic hypoxia was studied in 16 anesthetized dogs. Sympathetic activity was altered by clamping the carotid arteries bilaterally below the carotid sinus. One group (n = 8) was beta blocked by administration of propranolol (1 mg/kg); a second group (n = 8) was untreated. Venous outflow from the left hindlimb was isolated for measurement of blood flow and O2 uptake (VO2). After a 20-min control period, both carotid arteries were clamped (CC) for 20 min followed by a 20-min recovery period. The sequence was repeated after hematocrit was lowered to about 15% by dextran exchange for blood. Prior to anemia, CC did not alter cardiac output or limb blood flow in either group. After induction of anemia, hindlimb resistance was higher with CC in the beta block than in the no block group. Both limb blood flow and VO2 fell in the beta-block group with CC during anemia. Beta block also prevented the additive increases in whole body VO2 seen with CC and induction of anemia. The data showed that the increased vasoconstrictor tone that was obtained with beta block during anemia was successful in redistributing the lower viscosity blood away from resting skeletal muscle, even to the point that muscle VO2 was decreased.     

Regulation of canine skeletal muscle and hindlimb blood flow in acute anemia

Redistribution of blood flow away from resting skeletal muscles does not occur during anemic hypoxia even when whole body oxygen uptake is not maintained. In the present study, the effects of sympathetic nerve stimulation on both skeletal muscle and hindlimb blood flow were studied prior to and during anemia in anesthetized, paralyzed, and ventilated dogs. In one series (skeletal muscle group, n = 8) paw blood flow was excluded by placing a tourniquet around the ankle; in a second series (hindlimb group, n = 8) no tourniquet was placed at the ankle. The distal end of the transected left sciatic nerve was stimulated to produce a maximal vasoconstrictor response for 4-min intervals at normal hematocrit (Hct.) and at 30 min of anemia (Hct. = 14%). Arterial blood pressure and hindlimb or muscle blood flow were measured; resistance and vascular hindrance were calculated. Nerve stimulation decreased blood flow (p less than 0.05) in the hindlimb and muscle groups at normal Hct. Blood flow rose (p less than 0.05) during anemia and was decreased (p less than 0.05) in both groups during nerve stimulation. However, the blood flow values in both groups during nerve stimulation in anemic animals were greater (p less than 0.05) than those at normal Hct. Hindlimb and muscle vascular resistance fell significantly during anemia and nerve stimulation produced a greater increase in vascular resistance at normal Hct. Vascular hindrance in muscle, but not hindlimb, was less during nerve stimulation in anemia than at normal Hct.(ABSTRACT TRUNCATED AT 250 WORDS)     

Oxygen uptake and blood flow in canine skeletal muscle during moderate and severe anemia

The metabolic and cardiovascular adjustments of the whole body and skeletal muscle were studied during moderate and severe acute anemia. In 15 anesthetized dogs, venous outflow from the gastrocnemius-plantaris muscle group was isolated. Cardiac output (QT) muscle blood flow (QM), total body and muscle oxygen uptake (VO2) were determined during a control period, and at 30 and 60 min of either (i) moderate anemia (n = 8) in which the mean hematocrit (Hct) was 25% or (ii) progressive anemia (n = 7) in which the mean Hct values were 25% at 30 min and 16% at 60 min of anemia. Muscle VO2, QT, and QM were increased in both groups at 30 min of anemia. By 60 min, QT and QM declined to preanemic control values in the moderate anemia group; whole body VO2 was maintained at the control level. Arterial oxygen transport was the same in the two groups at both 30 and 60 min of anemia despite the difference in Hct at 60 min. Muscle VO2 showed a further and similar rise in both groups between 30 and 60 min of anemia. These data show that the rise in muscle VO2 during acute anemia was not directly proportional to the degree of the hematocrit reduction. Further, the findings suggest that the muscle VO2 response was related to the decrease in arterial oxygen transport.     

Changes in muscle sympathetic nerve activity and calf blood flow during static handgrip exercise

To test the function of sympathetic vasco-constrictor nerves on blood flow in resting limbs during static muscle contraction, muscle sympathetic nerve activity (MSNA) to the leg muscle was recorded from the tibial nerve microneurographically before, during and after 2 min of static handgrip (SHG). Simultaneously, calf blood flow (CBF) was measured by strain gauge plethysmography. An increase in MSNA, a decrease in CBF and an increase in calf vascular resistance (CVR) in the same resting limb occurred concomitantly during SHG. However, the increase in CVR was blunted in the second minute of handgrip when MSNA was still increasing. The results indicated that the decrease of CBF during SHG reflects the increase in MSNA, while the dissociation between MSNA and CVR at the later period of SHG may be related to metabolic change produced by the vasoconstriction.     

Previous exercise attenuates muscle sympathetic activity and increases blood flow during acute euglycemic hyperinsulinemia.

Insulin infusion causes muscle vasodilation, despite the increase in sympathetic nerve activity. In contrast, a single bout of exercise decreases sympathetic activity and increases muscle blood flow during the postexercise period. We tested the hypothesis that muscle sympathetic activity would be lower and muscle vasodilation would be higher during hyperinsulinemia performed after a single bout of dynamic exercise. Twenty-one healthy young men randomly underwent two hyperinsulinemic euglycemic clamps performed after 45 min of seated rest (control) or bicycle exercise (50% of peak oxygen uptake). Muscle sympathetic nerve activity (MSNA, microneurography), forearm blood flow (FBF, plethysmography), blood pressure (BP, oscillometric method), and heart rate (HR, ECG) were measured at baseline (90 min after exercise or seated rest) and during hyperinsulinemic euglycemic clamps. Baseline glucose and insulin concentrations were similar in the exercise and control sessions. Insulin sensitivity was unchanged by previous exercise. During the clamp, insulin levels increased similarly in both sessions. As expected, insulin infusion increased MSNA, FBF, BP, and HR in both sessions (23 +/- 1 vs. 36 +/- 2 bursts/min, 1.8 +/- 0.1 vs. 2.2 +/- 0.2 ml.min(-1).100 ml(-1), 89 +/- 2 vs. 92 +/- 2 mmHg, and 58 +/- 1 vs. 62 +/- 1 beats/min, respectively, P < 0.05). BP and HR were similar between sessions. However, MSNA was significantly lower (27 +/- 2 vs. 31 +/- 2 bursts/min), and FBF was significantly higher (2.2 +/- 0.2 vs. 1.8 +/- 0.1 ml.min(-1).100 ml(-1), P < 0.05) in the exercise session compared with the control session. In conclusion, in healthy men, a prolonged bout of dynamic exercise decreases MSNA and increases FBF. These effects persist during acute hyperinsulinemia performed after exercise.     

Uterine artery blood flow and renal sympathetic nerve activity during exercise in rabbit pregnancy

The uterine artery blood flow (UtBF) and renal sympathetic nerve activity (SNA) responses to treadmill exercise were evaluated in 12 nonpregnant (NP) and 17 term pregnant (P) rabbits. UtBF was monitored continuously with a Transonic flowprobe. Rabbits underwent three exercise trials (5-min duration) that varied in absolute workload. The rise in renal SNA with exercise was intensity related. Pregnancy did not affect the average steady-state renal SNA response expressed relative to maximum activity (P 24 +/- 1% vs. NP 23 +/- 2% of maximum smoke-elicited activity) and increased the average renal SNA response expressed relative to resting activity (P +155 +/- 19% vs. NP +84 +/- 23% from rest, P = 0.03) At rest, UtBF (P 13 +/- 3 vs. NP 1.9 +/- 0.3 ml/min) and uterine artery conductance (UtC; P 22 +/- 5 vs. NP 2.8 +/- 0.5 ml. min-1.mmHg-1 x 10-2) were elevated in the P rabbits. The average exercise-related decreases in UtBF (P -16 +/- 4% vs. NP -48 +/- 4%) and UtC (P -27 +/- 4% vs. NP -54 +/- 4%) were attenuated in the P rabbits. Pregnancy does not impair the ability to raise renal SNA but attenuates the uterine artery constrictor response to moderate to heavy dynamic exercise in rabbits. Under normal conditions, the pregnant uterine circulatory bed may be relatively protected from exercise-related redistribution of blood flow.     

Differential control of intrarenal blood flow during reflex increases in sympathetic nerve activity

The role of renal sympathetic nerve activity (RSNA) in the physiological regulation of medullary blood flow (MBF) remains ill defined, yet regulation of MBF may be crucial to long-term arterial pressure regulation. To investigate the effects of reflex increases in RSNA on intrarenal blood flow distribution, we exposed pentobarbital sodium-anesthetized, artificially ventilated rabbits (n = 7) to progressive hypoxia while recording RSNA, cortical blood flow (CBF), and MBF using laser-Doppler flowmetry. Another group of animals with denervated kidneys (n = 6) underwent the same protocol. Progressive hypoxia (from room air to 16, 14, 12, and 10% inspired O(2)) significantly reduced arterial oxygen partial pressure (from 99 +/- 3 to 65 +/- 2, 51 +/- 2, 41 +/- 1, and 39 +/- 2 mmHg, respectively) and significantly increased RSNA (by 8 +/- 3, 44 +/- 25, 62 +/- 21, and 76 +/- 37%, respectively, compared with room air) without affecting mean arterial pressure. There were significant reductions in CBF (by 2 +/- 1, 5 +/- 2, 11 +/- 3, and 14 +/- 2%, respectively) in intact but not denervated rabbits. MBF was unaffected by hypoxia in either group. Thus moderate reflex increases in RSNA cause renal cortical vasoconstriction, but not at vascular sites regulating MBF.     

Alpha-adrenergic receptor-mediated restraint of skeletal muscle blood flow during prolonged exercise.

Sympathetic nervous system restraint of skeletal muscle blood flow during dynamic exercise has been well documented. However, whether sympathetic restraint of muscle blood flow persists and is constant throughout prolonged exercise has not been established. We hypothesized that both alpha1- and alpha2-adrenergic receptors would restrain skeletal muscle blood flow throughout prolonged constant-load exercise and that the restraint would increase as a function of exercise duration. Mongrel dogs were instrumented chronically with transit-time flow probes on the external iliac arteries and an indwelling catheter in a branch of the femoral artery. Flow-adjusted doses of selective alpha1- (prazosin) and alpha2-adrenergic receptor (rauwolscine) antagonists were infused after 5, 30, and 50 min of treadmill exercise at 3 and 6 miles/h. During mild-intensity exercise (3 miles/h), prazosin infusion resulted in a greater (P < 0.05) increase in vascular conductance (VC) after 5 [42% (SD 6)], compared with 30 [28% (SD 6)] and 50 [28% (SD 8)] min of running. In contrast, prazosin resulted in a similar increase in VC after 5 [29% (SD 10)], 30 [24% (SD 9)], and 50 [22% (SD 9)] min of moderate-intensity (6 miles/h) exercise. Rauwolscine infusion resulted in a greater (P < 0.05) increase in VC after 5 [39% (SD 14)] compared with 30 [26% (SD 9)] and 50 [22% (SD 4)] min of exercise at 3 miles/h. Rauwolscine infusion produced a similar increase in VC after 5 [19% (SD 3)], 30 [15% (SD 6)], and 50 [16% (SD 2)] min of exercise at 6 miles/h. These results suggest that the ability of alpha1- and alpha2-adrenergic receptors to produce vasoconstriction and restrain blood flow to active muscles may be influenced by both the intensity and duration of exercise.     

Relationship between renal sympathetic nerve activity and renal blood flow during natural behavior in rats

The purpose of the present study was to determine the relationship between renal sympathetic nerve activity (RSNA) and renal blood flow (RBF) during normal daily activity in conscious, chronically instrumented Wistar rats (n = 8). The animal's behavior was classified as rapid eye movement (REM) sleep, non-REM (NREM) sleep, quiet awake, moving, and grooming states. On average RSNA was lowest during REM sleep, which was decreased by 39.0 +/- 3.2% (P < 0.05) relative to NREM sleep, and rose linearly with an increase in activity level in the order of quiet awake (by 10.9 +/- 1.8%, P < 0.05), moving (by 29.4 +/- 2.9%, P < 0.05), and grooming (by 65.3 +/- 3.9%, P < 0.05) relative to NREM sleep. By contrast, RBF was highest during REM sleep, which was increased by 4.8 +/- 0.7% (P < 0.05) relative to NREM sleep and decreased significantly (P < 0.05) by 5.5 +/- 0.6 and 6.6 +/- 0.5% during moving and grooming states, respectively, relative to NREM sleep. There was a significant (P < 0.05) inverse linear relationship between the percent changes in RSNA and RBF and between those in RSNA and renal vascular conductance. Furthermore, renal denervation (n = 8) abolished the changes in RBF induced by different natural behavioral activities. These results suggest that the changes in RSNA induced by natural behavioral activities had a significant influence on RBF.     

A theory of blood flow in skeletal muscle

A theoretical analysis of blood flow in the microcirculation of skeletal muscle is provided. The flow in the microvessels of this organ is quasi steady and has a very low Reynolds number. The blood is non-Newtonian and the blood vessels are distensible with viscoelastic properties. A formulation of the problem is provided using a viscoelastic model for the vessel wall which was recently derived from measurements in the rat spinotrapezius muscle (Skalak and Schmid-Sch?nbein, 1986b). Closed form solutions are derived for several physiologically important cases, such as perfusion at steady state, transient and oscillatory flows. The results show that resting skeletal muscle has, over a wide range of perfusion pressures an almost linear pressure-flow curve. At low flow it exhibits nonlinearities. Vessel distensibility and the non-Newtonian properties of blood both have a strong influence on the shape of the pressure-flow curve. During oscillatory flow the muscle exhibits hysteresis. The theoretical results are in qualitative agreement with experimental observations.     

Adrenoceptor regulation of canine skeletal muscle blood flow during carbon monoxide hypoxia.

We questioned whether carbon monoxide hypoxia (COH) would affect peripheral blood flow by neural activation of adrenoceptors to the extent we had found in other forms of hypoxia. We studied this problem in hindlimb muscles of four groups of anesthetized dogs (untreated, alpha 1-blocked, alpha 1 + alpha 2-blocked, and beta 2-blocked). Cardiac output increased, but hindlimb blood flow (QL) and resistance (RL) remained at prehypoxic levels during COH (O2 content reduced 50%) in untreated animals. When activity in the sciatic nerve was reversibly cold blocked, QL doubled and RL decreased 50%. These changes with nerve block were the same during COH, suggesting that neural activity to hindlimb vasculature was not increased by COH. In animals treated with phenoxybenzamine (primarily alpha 1-blocked), RL dropped (approximately 50%) during COH, an indication that catecholamines played a significant role in maintaining tone to skeletal muscle. Animals with both alpha 1 + alpha 2-adrenergic blockade (phenoxybenzamine and yohimbine added) did not survive COH. RL was higher in beta 2-block than in the untreated group during COH, but nerve cooling indicated that beta 2-adrenoceptor vasodilation was accomplished primarily by humoral means. The above findings demonstrated that adrenergic receptors were important in the regulation of QL and RL during COH, but they were not activated by sympathetic nerve stimulation to the limb muscles.     

Local control of skeletal muscle blood flow during exercise: influence of available oxygen

Reductions in oxygen availability (O(2)) by either reduced arterial O(2) content or reduced perfusion pressure can have profound influences on the circulation, including vasodilation in skeletal muscle vascular beds. The purpose of this review is to put into context the present evidence regarding mechanisms responsible for the local control of blood flow during acute systemic hypoxia and/or local hypoperfusion in contracting muscle. The combination of submaximal exercise and hypoxia produces a "compensatory" vasodilation and augmented blood flow in contracting muscles relative to the same level of exercise under normoxic conditions. A similar compensatory vasodilation is observed in response to local reductions in oxygen availability (i.e., hypoperfusion) during normoxic exercise. Available evidence suggests that nitric oxide (NO) contributes to the compensatory dilator response under each of these conditions, whereas adenosine appears to only play a role during hypoperfusion. During systemic hypoxia the NO-mediated component of the compensatory vasodilation is regulated through a β-adrenergic receptor mechanism at low-intensity exercise, while an additional (not yet identified) source of NO is likely to be engaged as exercise intensity increases during hypoxia. Potential candidates for stimulating and/or interacting with NO at higher exercise intensities include prostaglandins and/or ATP. Conversely, prostaglandins do not appear to play a role in the compensatory vasodilation during exercise with hypoperfusion. Taken together, the data for both hypoxia and hypoperfusion suggest NO is important in the compensatory vasodilation seen when oxygen availability is limited. This is important from a basic biological perspective and also has pathophysiological implications for diseases associated with either hypoxia or hypoperfusion.     

Hindlimb unloading increases oxidative stress and disrupts antioxidant capacity in skeletal muscle

Skeletal muscle disuse with space-flight and ground-based models (e.g., hindlimb unloading) results in dramatic skeletal muscle atrophy and weakness. Pathological conditions that cause muscle wasting (i.e., heart failure, muscular dystrophy, sepsis, COPD, cancer) are characterized by elevated "oxidative stress," where antioxidant defenses are overwhelmed by oxidant production. However, the existence, cellular mechanisms, and ramifications of oxidative stress in skeletal muscle subjected to hindlimb unloading are poorly understood. Thus we examined the effects of hindlimb unloading on hindlimb muscle antioxidant enzymes (e.g., superoxide dismutase, catalase, glutathione peroxidase), nonenzymatic antioxidant scavenging capacity (ASC), total hydroperoxides, and dichlorohydrofluorescein diacetate (DCFH-DA) oxidation, a direct indicator of oxidative stress. Twelve 6 month old Sprague Dawley rats were divided into two groups: 28 d of hindlimb unloading (n = 6) and controls (n = 6). Hindlimb unloading resulted in a small decrease in Mn-superoxide dismutase activity (10.1%) in the soleus muscle, while Cu,Zn-superoxide dismutase increased 71.2%. In contrast, catalase and glutathione peroxidase, antioxidant enzymes that remove hydroperoxides, were significantly reduced in the soleus with hindlimb unloading by 54.5 and 16.1%, respectively. Hindlimb unloading also significantly reduced ASC. Hindlimb unloading increased soleus lipid hydroperoxide levels by 21.6% and hindlimb muscle DCFH-DA oxidation by 162.1%. These results indicate that hindlimb unloading results in a disruption of antioxidant status, elevation of hydroperoxides, and an increase in oxidative stress.     

Nitric oxide and prostaglandins influence local skeletal muscle blood flow during exercise in humans: coupling between local substrate uptake and blood flow

Synergic action of nitric oxide (NO) and prostaglandins (PG) in the regulation of muscle blood flow during exercise has been demonstrated. In the present study, we investigated whether these vasodilators also regulate local blood flow, flow heterogeneity, and glucose uptake within the exercising skeletal muscle. Skeletal muscle blood flow was measured in seven healthy young men using near-infrared spectroscopy and indocyanine green and muscle glucose uptake using positron emission tomography and 2-fluoro-2-deoxy-D-[(18)F]glucose without and with local blockade of NO and PG at rest and during one-legged dynamic knee-extension exercise. Local blockade was produced by infusing nitro-L-arginine methyl ester and indomethacin directly in the muscle via a microdialysis catheter. Blood flow and glucose uptake were measured in the region of blockade and in two additional regions of vastus lateralis muscle 1 and 4 cm away from the infusion of blockers. Local blockade during exercise at 25 and 40 watts significantly decreased blood flow in the infusion region and in the region 1 cm away from the site of infusion but not in the region 4 cm away. During exercise, muscle glucose uptake did not show any regional differences in response to blockade. These results show that NO and PG synergistically contribute to the local regulation of blood flow in skeletal muscle independently of muscle glucose uptake in healthy young men. Thus these vasodilators can play a role in regulating microvascular blood flow in localized regions of vastus lateralis muscle but do not influence regional glucose uptake. The findings suggest that local substrate uptake in skeletal muscle can be regulated independently of regional changes in blood flow.     

Effect of sustained limb ischemia on norepinephrine release from skeletal muscle sympathetic nerve endings

Acute ischemia has been reported to impair sympathetic outflow distal to the ischemic area in various organs, whereas relatively little is known about this phenomenon in skeletal muscle. We examined how acute ischemia affects norepinephrine (NE) release at skeletal muscle sympathetic nerve endings. We implanted a dialysis probe into the adductor muscle in anesthetized rabbits and measured dialysate NE levels as an index of skeletal muscle interstitial NE levels. Regional ischemia was introduced by microsphere injection and ligation of the common iliac artery. The time courses of dialysate NE levels were examined during prolonged ischemia. Ischemia induced a decrease in the dialysate NE level (from 19+/-4 to 2.0+/-0 pg/ml, mean+/-S.E.), and then a progressive increase in the dialysate NE level. The increment in the dialysate NE level was examined with local administration of desipramine (DMI, a membrane NE transport inhibitor), omega-conotoxin GVIA (CTX, an N-type Ca(2+) channel blocker), or TMB-8 (an intracellular Ca(2+) antagonist). At 4h ischemia, the increment in the dialysate NE level (vehicle group, 143+/-30 pg/ml) was suppressed by TMB-8 (25+/-5 pg/ml) but not by DMI (128+/-10 pg/ml) or CTX (122+/-18 pg/ml). At 6h ischemia, the increment in the dialysate NE level was not suppressed by the pretreatment. Ischemia induced biphasic responses in the skeletal muscle. Initial reduction of NE release may be mediated by an impairment of axonal conduction and/or NE release function, while in the later phase, the skeletal muscle ischemia-induced NE release was partly attributable to exocytosis via intracellular Ca(2+) overload rather than opening of calcium channels or carrier mediated outward transport of NE.     

Involvement of sympathetic nerve activity in skin blood flow oscillations in humans

We have used the wavelet transform to evaluate the time-frequency content of laser-Doppler flowmetry (LDF) signals measured simultaneously on the surfaces of free microvascular flaps deprived of sympathetic nerve activity (SNA), and on adjacent intact skin, in humans. It was thereby possible to determine the frequency interval within which SNA manifests itself in peripheral blood flow oscillations. The frequency interval from 0.0095 to 2 Hz was examined and was divided into five subintervals: I, approximately 0.01 Hz; II, approximately 0.04 Hz; III, approximately 0.1 Hz; IV, approximately 0.3 Hz; and V, approximately 1 Hz. The average value of the LDF signal in the time domain as well as the mean amplitude and total power in the interval from 0.0095 to 2 Hz and amplitude and power within each of the five subintervals were significantly lower for signals measured on the free flap (P < 0.002). The normalized spectral amplitude and power in the free flap were significantly lower in only two intervals: I, from 0.0095 to 0.021 Hz; and II, from 0.021 to 0.052 Hz (P < 0.05); thus indicating that SNA is manifested in at least one of these frequency intervals. Because interval I has recently been shown to be the result of vascular endothelial activity, we conclude that we have identified SNA as influencing blood flow oscillations in normal tissues with repetition times of 20-50 s or frequencies of 0.02-0.05 Hz.     

The critical role of VEGF in skeletal muscle angiogenesis and blood flow

VEGF (vascular endothelial growth factor) is well known as an important molecule in angiogenesis. Its inhibition is pursued as an anticancer therapy; its enhancement as therapy for tissue ischaemia. In the present paper, its role in skeletal muscle is explored, both at rest and after exercise. Muscle VEGF mRNA and protein are increased severalfold after heavy exercise. Whereas global VEGF knockout is embryonically lethal, muscle-specific knockout is not, providing models for studying its functional significance. Its deletion in adult mouse skeletal muscle: (i) reduces muscle capillarity by more than 50%, (ii) decreases exercise endurance time by approximately 80%, and (iii) abolishes the angiogenic response to exercise training. What causes VEGF to increase with exercise is not clear. Despite regulation by HIF (hypoxia-inducible factor), increased HIF on exercise, and PO2 falling to single digit values during exercise, muscle-specific HIF knockout does not impair performance or capillarity, leaving many unanswered questions.     

Baroreflex control of muscle sympathetic nerve activity during skin surface cooling.

Skin surface cooling improves orthostatic tolerance through a yet to be identified mechanism. One possibility is that skin surface cooling increases the gain of baroreflex control of efferent responses contributing to the maintenance of blood pressure. To test this hypothesis, muscle sympathetic nerve activity (MSNA), arterial blood pressure, and heart rate were recorded in nine healthy subjects during both normothermic and skin surface cooling conditions, while baroreflex control of MSNA and heart rate were assessed during rapid pharmacologically induced changes in arterial blood pressure. Skin surface cooling decreased mean skin temperature (34.9 +/- 0.2 to 29.8 +/- 0.6 degrees C; P < 0.001) and increased mean arterial blood pressure (85 +/- 2 to 93 +/- 3 mmHg; P < 0.001) without changing MSNA (P = 0.47) or heart rate (P = 0.21). The slope of the relationship between MSNA and diastolic blood pressure during skin surface cooling (-3.54 +/- 0.29 units.beat(-1).mmHg(-1)) was not significantly different from normothermic conditions (-2.94 +/- 0.21 units.beat(-1).mmHg(-1); P = 0.19). The slope depicting baroreflex control of heart rate was also not altered by skin surface cooling. However, skin surface cooling shifted the "operating point" of both baroreflex curves to high arterial blood pressures (i.e., rightward shift). Resetting baroreflex curves to higher pressure might contribute to the elevations in orthostatic tolerance associated with skin surface cooling.