No effect of systemic isocapnic hypoxia on α-adrenergic vasoconstrictor responsiveness in human skin.

UNLABELLED: Hypoxia impairs body temperature regulation and abolishes the decline in skin temperature associated with cold exposure, suggesting that cutaneous vasoconstriction is impaired. AIM: The purpose of this study was to test the hypothesis that cutaneous vasoconstriction to intradermal tyramine, an index of post-junctional vasoconstrictor responsiveness, is reduced during hypoxia. METHODS: Twelve subjects (six males, six females) had three microdialysis fibres placed in the ventral forearm. Fibres received either lactated ringers, 5 mm yohimbine (α-adrenergic blockade), or 10.5 µm BIBP-3226 (to antagonize neuropeptide Y Y(1) receptors). Skin blood flow was assessed at each site (laser-Doppler flowmetry) and cutaneous vascular conductance (CVC) was calculated (red blood cell flux/mean arterial pressure) and scaled to baseline. Vasoconstrictor responses to tyramine (173 µm) were tested during normoxia and steady-state isocapnic hypoxia (SaO(2) = 80%) in random order. RESULTS: During normoxia, tyramine reduced CVC by 56.0±5.6 and 50.3±8.0% in control and BIBP-3226 sites (both P<0.05 vs. pre-tyramine; P=0.445 between sites) whereas CVC in the yohimbine site did not change (P=0.398 vs. pre-tyramine). During isocapnic hypoxia, tyramine reduced CVC by 55.9±5.1 and 54.2±5.4% in control and BIBP-3226 sites (both P<0.05 vs. pre-tyramine; P=0.814 between sites) whereas CVC was unchanged in the yohimbine site (P=0.732 vs. pre-tyramine). Isocapnic hypoxia did not affect vasoconstrictor responses at any site (all P>0.05 vs. normoxia). CONCLUSION: We conclude that post-junctional α-adrenergic vasoconstrictor responsiveness is not affected by hypoxia in non-acral skin.

Digital thermal hyperaemia impairment does not relate to skin fibrosis or macrovascular disease in systemic sclerosis.

OBJECTIVES: Thermal hyperaemia is impaired in patients with systemic sclerosis (SSc). The objective of these studies was to determine whether this was consecutive to skin fibrosis, microangiopathy or macroangiopathy. METHODS: Using laser Doppler flowmetry, we first compared the thermal hyperaemia on the third left finger pad and on the left forearm in 21 patients with non-diffuse systemic sclerosis (SSc), in comparison with primary Raynaud's phenomenon and healthy volunteers. Second, we tested whether the altered thermal hyperaemia correlated to the digital pressure index at baseline, and following the thermal challenge. RESULTS: In the first study, thermal hyperaemia of the finger pad was impaired in terms of both amplitude and kinetics, but not on the forearm in patients with SSc. In the seven SSc patients without cutaneous fibrosis, the response was similarly altered in terms of amplitude and kinetics. In the second study, we observed a weak correlation between the digital systolic blood pressure index. However, in the 15 SSc patients tested at 44 degrees C, the median digital systolic blood pressure index was 1.04 (0.84-1.24) at baseline vs 1.08 (0.87-1.29) at 44 degrees C (NS), while seven of them had an abnormal response in terms of kinetic. Furthermore, only one patient showed a clear-cut decrease in digital systolic blood pressure at 44 degrees C. CONCLUSION: In patients with SSc, digital thermal hyperaemia is impaired, but does not relate to the skin fibrosis or to an associated macroangiopathy in most cases. Further studies are required to determine whether its impairment reflects a functional or structural microvascular damage.

Cutaneous vascular function during acute hyperglycemia in healthy young adults.

Although it is well established that severe chronic hyperglycemia is associated with microvascular disease, it is not known whether transient hyperglycemia similar to that observed with impaired glucose tolerance or early Type 2 diabetes contributes to this pathology by altering microvascular function. To test the hypothesis that acute hyperglycemia decreases microvascular vasodilator responsiveness in human skin, we measured the cutaneous vasodilator response to local warming. This response can be divided into two phases, an initial peak that relies predominantly on local sensory nerves and a second slower phase that is largely dependent on endothelial nitric oxide. We reasoned that a change in one or both phases would indicate a change in the corresponding mechanism(s) with hyperglycemia. Twenty-eight healthy volunteers (14 women, 14 men) were randomly divided into three groups, corresponding to 6 h of euglycemia (n = 8), 6 h when glucose was clamped at approximately 7 mmol/l (n = 10), or 6 h when glucose was varied to mimic a postprandial pattern (i.e., peak glucose approximately 11.1 mmol/l) commonly observed in individuals with impaired glucose tolerance (n = 10). Insulin concentrations in all instances were maintained at approximately 65 pmol/l by means of continuous infusions of somatostatin and insulin. Glucagon and growth hormone were also continuously infused to maintain their basal concentrations. Despite substantial differences in both the level and pattern of glucose concentrations, neither maximum cutaneous vasodilation nor the pattern of the vasodilator response to local warming differed over the 6 h of study. We conclude that acute hyperglycemia similar to levels commonly observed in people with either early Type 2 diabetes or impaired glucose tolerance does not alter the vasodilator response to local warming of the skin in humans.

Effects of regional phentolamine on hypoxic vasodilatation in healthy humans.

1. Limb vascular beds exhibit a graded dilatation in response to hypoxia despite increased sympathetic vasoconstrictor nerve activity. We investigated the extent to which sympathetic vasoconstriction can mask hypoxic vasodilatation and assessed the relative contributions of beta-adrenergic and nitric oxide (NO) pathways to hypoxic vasodilatation. 2. We measured forearm blood flow responses (plethysmography) to isocapnic hypoxia (arterial saturation approximately 85%) in eight healthy men and women (18-26 years) after selective alpha-adrenergic blockade (phentolamine) of one forearm. Subsequently, we measured hypoxic responses after combined alpha- and beta-adrenergic blockade (phentolamine and propranolol) and after combined alpha- and beta-adrenergic blockade coupled with NO synthase inhibition (N(G)-monomethyl-L-arginine, L-NMMA). 3. Hypoxia increased forearm vascular conductance by 49.0 +/- 13.5% after phentolamine (compared to +16.8 +/- 7.0% in the control arm without phentolamine, P < 0.05). After addition of propranolol, the forearm vascular conductance response to hypoxia was reduced by approximately 50%, but dilatation was still present (+24.7 +/- 7.0%, P < 0.05 vs. normoxia). When L-NMMA was added, there was no further reduction in the forearm vascular conductance response to hypoxia (+28.2 +/- 4.0%, P < 0.05 vs. normoxia). 4. Thus, selective regional alpha-adrenergic blockade unmasked a greater hypoxic vasodilatation than occurs in the presence of functional sympathetic nervous system responses to hypoxia. Furthermore, approximately half of the hypoxic vasodilatation in the forearm appears to be mediated by beta-adrenergic receptor-mediated pathways. Finally, since considerable dilatation persists in the presence of both beta-adrenergic blockade and NO synthase inhibition, it is likely that an additional vasodilator mechanism is activated by hypoxia in humans.

Reduced submaximal leg blood flow after high-intensity aerobic training.

This study evaluated the hypothesis that active muscle blood flow is lower during exercise at a given submaximal power output after aerobic conditioning as a result of unchanged cardiac output and blunted splanchnic vasoconstriction. Eight untrained subjects (4 men, 4 women, 23-31 yr) performed high-intensity aerobic training for 9-12 wk. Leg blood flow (femoral vein thermodilution), splanchnic blood flow (indocyanine green clearance), cardiac output (acetylene rebreathing), whole body O(2) uptake (VO(2)), and arterial-venous blood gases were measured before and after training at identical submaximal power outputs (70 and 140 W; upright 2-leg cycling). Training increased (P < 0.05) peak VO(2) (12-36%) but did not significantly change submaximal VO(2) or cardiac output. Leg blood flow during both submaximal power outputs averaged 18% lower after training (P = 0.001; n = 7), but these reductions were not correlated with changes in splanchnic vasoconstriction. Submaximal leg VO(2) was also lower after training. These findings support the hypothesis that aerobic training reduces active muscle blood flow at a given submaximal power output. However, changes in leg and splanchnic blood flow resulting from high-intensity training may not be causally linked.

Nitric oxide and neurally mediated regulation of skin blood flow during local heating.

The mechanisms underlying the skin blood flow (SkBF) response to local heating are complex and poorly understood. Our goal was to examine the role of axon reflexes and nitric oxide (NO) in the SkBF response to a local heating protocol. We performed 40 experiments following a standardized heating protocol with different interventions, including blockade of the axon reflex (EMLA cream), antebrachial nerve blockade (0.5% bupivacaine injection), and NO synthase (NOS) inhibition (> or =10 mM N(G)-nitro-L-arginine methyl ester; microdialysis). Appropriate controls were performed to verify the efficacy of the various blocks. Values are expressed as a percentage of maximal SkBF (SkBF(max); 50 mM sodium nitroprusside). At the initiation of local heating, SkBF rose to an initial peak, followed by a brief nadir, and a secondary, progressive rise to a plateau. Axon reflex block decreased the initial peak from 75+3 to 32 +/- 2% SkBF(max) (P < 0.01 vs. control) but did not affect the plateau. NOS inhibition before and throughout local heating reduced the initial peak from 75 +/- 3 to 56 +/- 3% SkBF(max) (P < 0.01) and the plateau from 87 +/- 4 to 40 +/- 5%. NOS inhibition during axon reflex block did not further reduce the initial SkBF peak compared with axon reflex block alone. Antebrachial nerve block did not affect the local heating SkBF response. The primary finding of these studies is that there are at least two independent mechanisms contributing to the rise in SkBF during nonpainful local heating: a fast-responding vasodilator system mediated by the axon reflexes and a more slowly responding vasodilator system that relies on local production of NO.

beta-Receptor agonist activity of phenylephrine in the human forearm.

Phenylephrine is generally regarded as a "pure" alpha(1)-agonist. However, after treatment of the forearm with the alpha-adrenergic-blocking drug phentolamine, brachial artery infusion of phenylephrine can cause transient forearm vasodilation. To determine whether this response was beta-receptor mediated, phenylephrine, phentolamine, and propranolol were infused into the brachial arteries of six healthy volunteers. Forearm vascular conductance (FVC) was also calculated and expressed as arbitrary units (units). Infusion of phenylephrine by itself (0.5 microg. dl forearm volume(-1). min(-1)) caused a sustained decrease (P < 0.05) in FVC from 3.5 +/- 0.7 to 0.9 +/- 0.2 units (P < 0.05). Infusion of the alpha-blocker phentolamine increased (P < 0.05) baseline FVC to 5.7 +/- 1.3 units. Subsequent infusion of phenylephrine after alpha-blockade caused FVC to increase (P < 0.05) for ~1 min from 5.7 +/- 1.3 to a peak of 13.1 +/- 1.8 units. Propranolol had no effect on baseline flow, and subsequent phenylephrine infusion after alpha- and beta-blockade caused a small, but significant, sustained decrease in FVC from 5.1 +/- 1.0 to 3.6 +/- 0.8 units. There were no systemic effects from the infusions, and saline infusion at the same rate (1-2 ml/min) had no forearm vasoconstrictor or dilator effects. These data indicate that in humans phenylephrine can exert transient beta(2)-vasodilator activity when its predominant alpha-constrictor effects are blocked.

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

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

Sympathetic activity and baroreflex sensitivity in young women taking oral contraceptives.

BACKGROUND: We tested sympathetic and cardiovagal baroreflex sensitivity during the placebo or "low-hormone" phase (LH) and 2 to 3 weeks later during the "high-hormone" phase (HH) of oral contraceptive (OC) use in 9 women. METHODS AND RESULTS: Sympathetic baroreflex sensitivity was assessed by intravenous doses of sodium nitroprusside and phenylephrine and defined as the slope relating muscle sympathetic nerve activity (by microneurography) and diastolic blood pressure. Cardiovagal baroreflex sensitivity was defined as the slope relating R-R interval and systolic blood pressure. No difference was observed for resting muscle sympathetic nerve activity or plasma norepinephrine levels. However, sympathetic baroreflex sensitivity was greater and mean arterial pressure was higher during the LH than in the HH phase. Similarly, cardiovagal baroreflex sensitivity was greater in the LH than in the HH phase. CONCLUSIONS: Sympathetic and cardiovagal baroreflex sensitivities change during the 28-day course of OC use. Furthermore, changes in baroreflex sensitivity with OC differ from changes in baroreflex sensitivity during the normal menstrual cycle.

Skeletal muscle vasodilatation during sympathoexcitation is not neurally mediated in humans.

Evidence for the existence of sympathetic vasodilator nerves in human skeletal muscle is controversial. Manoeuvres such as contralateral ischaemic handgripping to fatigue that cause vasoconstriction in the resting forearm evoke vasodilatation after local alpha-adrenergic receptor blockade, raising the possibility that both constrictor and dilator fibres are present. The purpose of this study was to determine whether this dilatation is neurally mediated. Ten subjects (3 women, 7 men) performed ischaemic handgripping to fatigue before and after acute local anaesthetic block of the sympathetic nerves (stellate ganglion) innervating the contralateral (resting) upper extremity. Forearm blood flow was measured with venous occlusion plethysmography in the resting forearm. In control studies there was forearm vasoconstriction during contralateral handgripping to fatigue. During contralateral handgripping after stellate block, blood flow in the resting forearm increased from 6.1 +/- 0.7 to 18.7 +/- 2.2 ml dl-1 min-1 (P < 0.05). Mean arterial pressure measured concurrently increased from approximately 90 to 130 mmHg and estimated vascular conductance rose from 6.5 +/- 0.7 to 14.0 +/- 1.5 units, indicating that most of the rise in forearm blood flow was due to vasodilatation. Brachial artery administration of beta-blockers (propranolol) and the nitric oxide (NO) synthase inhibitor N G-monomethyl-L-arginine (L-NMMA) after stellate block virtually eliminated all of the vasodilatation to contralateral handgrip. Since vasodilatation was seen after stellate block, our data suggest that sympathetic dilator nerves are not responsible for limb vasodilatation seen during sympathoexcitation evoked by contralateral ischaemic handgripping to fatigue. The results obtained with propranolol and L-NMMA suggest that beta-adrenergic mechanisms and local NO release contribute to the dilatation.

Influence of the menstrual cycle on sympathetic activity, baroreflex sensitivity, and vascular transduction in young women.

BACKGROUND: Our goal was to test sympathetic and cardiovagal baroreflex sensitivity and the transduction of sympathetic traffic into vascular resistance during the early follicular (EF) and midluteal (ML) phases of the menstrual cycle. METHODS AND RESULTS: Sympathetic baroreflex sensitivity was assessed by lowering and raising blood pressure with intravenous bolus doses of sodium nitroprusside and phenylephrine. It was defined as the slope relating muscle sympathetic nerve activity (MSNA; determined by microneurography) and diastolic blood pressure. Cardiovagal baroreflex sensitivity was defined as the slope relating R-R interval and systolic blood pressure. Vascular transduction was evaluated during ischemic handgrip exercise and postexercise ischemia, and it was defined as the slope relating MSNA and calf vascular resistance (determined by plethysmography). Resting MSNA (EF, 1170+/-151 U/min; ML, 2252+/-251 U/min; P<0.001) and plasma norepinephrine levels (EF, 240+/-21 pg/mL; ML, 294+/-25 pg/mL; P=0. 025) were significantly higher in the ML than in the EF phase. Furthermore, sympathetic baroreflex sensitivity was greater during the ML than the EF phase in every subject (MSNA/diastolic blood pressure slopes: EF, -4.15; FL, -5.42; P=0.005). No significant differences in cardiovagal baroreflex sensitivity or vascular transduction were observed. CONCLUSIONS: The present study suggests that the hormonal fluctuations that occur during the normal menstrual cycle may alter sympathetic outflow but not the transduction of sympathetic activity into vascular resistance.

Effects of atropine and L-NAME on cutaneous blood flow during body heating in humans.

We sought to investigate further the roles of sweating, ACh spillover, and nitric oxide (NO) in the neurally mediated cutaneous vasodilation during body heating in humans. Six subjects were heated with a water-perfused suit while cutaneous blood flow was measured with a laser-Doppler flowmeter. After a rise in core temperature (1. 0 +/- 0.1 degrees C) and the establishment of cutaneous vasodilation, atropine and subsequently the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) were given to the forearm via a brachial artery catheter. After atropine infusion, cutaneous vascular conductance (CVC) remained constant in five of six subjects, whereas L-NAME administration blunted the rise in CVC in three of six subjects. A subsequent set of studies using intradermal microdialysis probes to selectively deliver drugs into forearm skin confirmed that atropine did not affect CVC. However, perfusion of L-NAME resulted in a significant decrease in CVC (37 +/- 4%, P < 0.05). The results indicate that neither sweating nor NO release via muscarinic receptor activation is essential to sustain cutaneous dilation during heating in humans.

Measurement of limb venous compliance in humans: technical considerations and physiological findings.

We conducted a series of studies to develop and test a rapid, noninvasive method to measure limb venous compliance in humans. First, we measured forearm volume (mercury-in-Silastic strain gauges) and antecubital intravenous pressure during inflation of a venous collecting cuff around the upper arm. Intravenous pressure fit the regression line, -0.3 +/- 0.7 + 0.95 +/- 0.02. cuff pressure (r = 0.99 +/- 0.00), indicating cuff pressure is a good index of intravenous pressure. In subsequent studies, we measured forearm and calf venous compliance by inflating the venous collecting cuff to 60 mmHg for 4 min, then decreasing cuff pressure at 1 mmHg/s (over 1 min) to 0 mmHg, using cuff pressure as an estimate of venous pressure. This method produced pressure-volume curves fitting the quadratic regression (Deltalimb volume) = beta(0) + beta(1). (cuff pressure) + beta(2). (cuff pressure)(2), where Delta is change. Curves generated with this method were reproducible from day to day (coefficient of variation: 4.9%). In 11 subjects we measured venous compliance via this method under two conditions: with and without (in random order) superimposed sympathetic activation (ischemic handgrip exercise to fatigue followed by postexercise ischemia). Calf and forearm compliance did not differ between control and sympathetic activation (P > 0.05); however, the data suggest that unstressed volume was reduced by the maneuver. These studies demonstrate that venous pressure-volume curves can be generated both rapidly and noninvasively with this technique. Furthermore, the results suggest that although whole-limb venous compliance is under negligible sympathetic control in humans, unstressed volume can be affected by the sympathetic nervous system.

Age, splanchnic vasoconstriction, and heat stress during tilting.

During upright tilting, blood is translocated to the dependent veins of the legs and compensatory circulatory adjustments are necessary to maintain arterial pressure. For examination of the effect of age on these responses, seven young (23 +/- 1 yr) and seven older (70 +/- 3 yr) men were head-up tilted to 60 degrees in a thermoneutral condition and during passive heating with water-perfused suits. Measurements included heart rate (HR), cardiac output (Qc; acetylene rebreathing technique), central venous pressure (CVP), blood pressures, forearm blood flow (venous occlusion plethysmography), splanchnic and renal blood flows (indocyanine green and p-aminohippurate clearance), and esophageal and mean skin temperatures. In response to tilting in the thermoneutral condition, CVP and stroke volume decreased to a greater extent in the young men, but HR increased more, such that the fall in Qc was similar between the two groups in the upright posture. The rise in splanchnic vascular resistance (SVR) was greater in the older men, but the young men increased forearm vascular resistance (FVR) to a greater extent than the older men. The fall in Qc during combined heat stress and tilting was greater in the young compared with older men. Only four of the young men versus six of the older men were able to finish the second tilt without becoming presyncopal. In summary, the older men relied on a greater increase in SVR to compensate for a reduced ability to constrict the skin and muscle circulations (as determined by changes in FVR) during head-up tilting.

Age alters the cardiovascular response to direct passive heating.

During direct passive heating in young men, a dramatic increase in skin blood flow is achieved by a rise in cardiac output (Qc) and redistribution of flow from the splanchnic and renal vascular beds. To examine the effect of age on these responses, seven young (Y; 23 +/- 1 yr) and seven older (O; 70 +/- 3 yr) men were passively heated with water-perfused suits to their individual limit of thermal tolerance. Measurements included heart rate (HR), Qc (by acetylene rebreathing), central venous pressure (via peripherally inserted central catheter), blood pressures (by brachial auscultation), skin blood flow (from increases in forearm blood flow by venous occlusion plethysmography), splanchnic blood flow (by indocyanine green clearance), renal blood flow (by p-aminohippurate clearance), and esophageal and mean skin temperatures. Qc was significantly lower in the older than in the young men (11.1 +/- 0.7 and 7.4 +/- 0.2 l/min in Y and O, respectively, at the limit of thermal tolerance; P < 0. 05), despite similar increases in esophageal and mean skin temperatures and time to reach the limit of thermal tolerance. A lower stroke volume (99 +/- 7 and 68 +/- 4 ml/beat in Y and O, respectively, P < 0.05), most likely due to an attenuated increase in inotropic function during heating, was the primary factor for the lower Qc observed in the older men. Increases in HR were similar in the young and older men; however, when expressed as a percentage of maximal HR, the older men relied on a greater proportion of their chronotropic reserve to obtain the same HR response (62 +/- 3 and 75 +/- 4% maximal HR in Y and O, respectively, P < 0.05). Furthermore, the older men redistributed less blood flow from the combined splanchnic and renal circulations at the limit of thermal tolerance (960 +/- 80 and 720 +/- 100 ml/min in Y and O, respectively, P < 0. 05). As a result of these combined attenuated responses, the older men had a significantly lower increase in total blood flow directed to the skin.

Age, fitness, and regional blood flow during exercise in the heat.

During dynamic exercise in warm environments, the requisite increase in skin blood flow (SkBF) is supported by an increase in cardiac output (Qc) and decreases in splanchnic (SBF) and renal blood flows (RBF). To examine interactions between age and fitness in determining this integrated response, 24 men, i.e., 6 younger fit (YF), 6 younger sedentary (YS), 6 older fit (OF), and 6 older sedentary (OS) rested for 50 min, then exercised at 35 and 60% maximal O2 consumption (VO2max) at 36 degrees C ambient temperature. YF had a significantly higher Qc and SkBF than any other group during exercise, but fitness level had no significant effect on any measured variable in the older men. At 60% VO2max, younger subjects had significantly greater decreases in SBF and RBF than the older men, regardless of fitness level. Total flow redirected from these two vascular beds (deltaSBF + deltaRBF) followed YF >> YS > OF > OS. A rigorous 4-wk endurance training program increased exercise SkBF in OS, but deltaSBF and deltaRBF were unchanged. Under these conditions, older men distribute Qc differently to regional circulations, i.e., smaller increases in SkBF and smaller decreases in SBF and RBF. In younger subjects, the higher SkBF associated with a higher fitness level is a function of both a higher Qc and a greater redistribution of flow from splanchnic and renal circulations, but the attenuated splanchnic and renal vasoconstriction in older men does not appear to change with enhanced aerobic fitness.

Age and cardiac output during cycle exercise in thermoneutral and warm environments.

To determine whether chronological age, independent of changes in aerobic capacity, alters cardiac output (Qc), the central hemodynamic responses to intermittent incremental cycle exercise were studied in two groups of men. Qc was measured at rest and during exercise at 35%, 60%, 75%, and 85% peak aerobic capacity (VO2peak) using a CO2 rebreathing method in seven trained older (65 +/- 2 yr) and eight normally active but untrained young men (26 +/- 1 yr) matched for VO2peak and anthropometric measures. Subjects were tested in both a thermoneutral (22 degrees C) and a warm (36 degrees C) environment to investigate possible differential cardiovascular responses to exercise in the heat. Only subjects with no history of pulmonary, cardiac, neuromuscular, or endocrine disease and a normal electrocardiogram were studied. The older men had significantly lower (P < 0.05) Qc relative to the younger men at intensities greater than 60% VO2peak in both environmental conditions. At these higher intensities, the older men had a significantly higher stroke volume (SV) and lower heart rate (HR) (P < 0.05). A higher arteriovenous oxygen difference ((a-v)O2)) compared with their younger counterparts enabled the older men to exercise at the same absolute intensity, most likely because of training induced changes in left-ventricular performance and oxygen extraction. The addition of an exogenous heat source did not alter the Qc response in either group of men; however, a higher HR (P < 0.05) and smaller SV (P > 0.05) were observed in the young men during exercise in the heat. This may reflect previously reported differences in the skin blood flow response of VO2peak-matched young and older men during exercise. It is suggested that endurance trained older men can enhance left-ventricular performance to augment SV, but not sufficiently to maintain Qc in light of an attenuated HR response during exercise at intensities above 60% VO2peak.