Hemodynamic and metabolic responses to exercise after adrenoceptor blockade in humans

The effects of acute alpha 1-adrenoceptor blockade with prazosin, beta 1-adrenoceptor blockade with atenolol, and nonselective beta-adrenoceptor blockade with propranolol were compared in a placebo-controlled crossover study of the hemodynamic and metabolic responses to acute exercise 2 h after prolonged prior exercise to induce skeletal muscle glycogen depletion, enhancing the dependence on hepatic glucose output and circulating free fatty acids (FFA). Plasma catecholamines were higher during exercise after, as opposed to before, glycogen depletion and were elevated further by all three drugs. Propranolol failed to produce a significant reduction in systolic blood pressure and elevated diastolic blood pressure. Atenolol reduced systolic blood pressure and did not change diastolic blood pressure. Both beta-blockers reduced FFA levels, but only propranolol lowered plasma glucose relative to placebo during exercise after glycogen depletion. In contrast, prazosin reduced systolic and diastolic blood pressures and resulted in elevated FFA and glucose levels. The results indicate important differences in the hemodynamic effects of beta 1-selective vs. nonselective beta-blockade during exercise after skeletal muscle glycogen depletion. Furthermore they confirm the importance of beta 2-mediated hepatic glucose production in maintaining plasma glucose levels during exercise. Acute alpha 1-blockade with prazosin induces reflex elevation of catecholamines, which in the absence of blockade of hepatic beta 2-receptors produces elevation of plasma glucose. The results suggest there is little role for alpha 1-mediated hepatic glucose production during exercise in humans.     

Ramp work tests with three different beta-blockers in normal human subjects

The effects of beta-blockade on the responses of oxygen uptake (VO2), heart rate (HR) and blood lactate (La-) were examined during ramp cycle ergometer tests (50 W.min-1 ramp slope) in 8 healthy male volunteers. Each subject took placebo, or one of four different doses of three different beta-blockers (propranolol, metoprolol or oxprenolol) 2 h prior to each test for a total of 15 exercise tests. VO2 was measured breath-by-breath, HR was sampled once per breath, and La- was obtained every minute. Linear regression analysis was applied to VO2 and HR data to obtain the kinetic parameter total lag time (TLT) and a slope value. La- was analyzed by a continuous exponential model with the lactate slope index (LSI) being derived from the individual response curves. Submaximal exercise HR was significantly depressed at the baseline as well as during the ramp tests by beta-blockade. TLT for HR was significantly affected by beta-blockade, with a dose dependent shift from a placebo value of 16 to 26 s with placebo to a value of -40 to -60 s at the highest dose. Slope of HR was significantly depressed relative to placebo. VO2 kinetics assessed by TLT were not significantly affected by beta-blockade. This slope of the VO2 vs work rate relationship was significantly less than placebo only at the highest dose of beta-blocker. The LSI was not significantly affected by beta-blockade. In contrast with the clear impairment of HR response to exercise during beta-blockade, both the VO2 and La- responses appear to be relatively unaffected by beta-blockade during ramp exercise tests.(ABSTRACT TRUNCATED AT 250 WORDS)     

Slower Adaptation of VO2 to steady state of submaximal exercise with beta-blockade

The kinetics of oxygen uptake (VO2) were assessed in 17 normal subjects with beta-blockade and placebo. beta-blockade was achieved with either 50 mg oral metoprolol or 40 mg oral propranolol, each twice per day. Tests were conducted on the cycle ergometer at work rates approximating 80% of the work rate at ventilatory anaerobic threshold. Work rate was initiated as a square wave starting from prior rest. Data obtained 48 h, 1 week, and 4 weeks after starting drug or placebo were pooled to increase the number of points for regression analysis of kinetic parameters. While there were no differences in the plateau values for VO2 with and without beta-blockade, the rate of adaptation to steady state was significantly slower with beta-blockade than with placebo (P less than 0.05). This resulted in an increase of oxygen deficit by approximately 200 ml O2. Cardiac output measured by CO2 rebreathing was significantly reduced by beta-blockade (metoprolol by 4.1%, propranolol by 12.2%, both P less than 0.05). Blood lactate concentration was unaffected by beta-blockade. It was concluded that the influence of beta-blockade on the oxygen transport system was responsible for the significantly slower increase of VO2 to steady state in submaximal exercise.     

Role of beta-adrenergic mechanisms during exercise in poorly controlled diabetes

To examine the beta-adrenergic effects of the catecholamines in poorly controlled diabetes, we have studied insulin-deprived alloxan-diabetic (A-D) dogs during 90 min of moderate exercise (100 m/min, 10-12 degrees) alone (C) or with propranolol (5 micrograms . kg-1 . min-1) (P) or combined P and somatostatin infusion (0.5 microgram . kg-1 . min-1) (P + St). In P, in contrast to C, immunoreactive glucagon (IRG) rose only after 50 min of exercise. However, hepatic glucose production (Ra) rose normally. In P + St, IRG fell 50% below basal, and the Ra response to exercise was abolished. Interestingly, in P and P + St, glucose metabolic clearance rate (MCR) rose by 400% above the inadequate MCR response to exercise in C, despite 30% lower insulin levels. Compared with C, free fatty acids (FFA) and lactate were sharply reduced during P and P + St. Plasma glucose (G) did not change in C, but due to elevated glucose uptake, G fell over 120 mg/dl in P, and due to diminished Ra, G fell 170 mg/dl in P + St. Norepinephrine was similar in all groups. Epinephrine and cortisol were higher in P + St by 90 min of exercise, perhaps as a result of hypoglycemia. In summary, during exercise in poorly controlled A-D dogs, beta-blockade does not appear to affect Ra; beta-blockade leads to diminished mobilization of extrahepatic substrate as evidenced by reduced FFA and lactate levels; beta-blockade increases MCR to levels seen in normal dogs during exercise alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pyruvate ingestion for 7 days does not improve aerobic performance in well-trained individuals.

The purposes of the present studies were to test the hypotheses that lower dosages of oral pyruvate ingestion would increase blood pyruvate concentration and that the ingestion of a commonly recommended dosage of pyruvate (7 g) for 7 days would enhance performance during intense aerobic exercise in well-trained individuals. Nine recreationally active subjects (8 women, 1 man) consumed 7, 15, and 25 g of pyruvate and were monitored for a 4-h period to determine whether blood metabolites were altered. Pyruvate consumption failed to significantly elevate blood pyruvate, and it had no effect on indexes of carbohydrate (blood glucose, lactate) or lipid metabolism (blood glycerol, plasma free fatty acids). As a follow-up, we administered 7 g/day of either placebo or pyruvate, for a 1-wk period to seven, well-trained male cyclists (maximal oxygen consumption, 62.3 +/- 3.0 ml. kg(-1). min(-1)) in a randomized, double-blind, crossover trial. Subjects cycled at 74-80% of their maximal oxygen consumption until exhaustion. There was no difference in performance times between the two trials (placebo, 91 +/- 9 min; pyruvate, 88 +/- 8 min). Measured blood parameters (insulin, peptide C, glucose, lactate, glycerol, free fatty acids) were also unaffected. Our results indicate that oral pyruvate supplementation does not increase blood pyruvate content and does not enhance performance during intense exercise in well-trained cyclists.     

Effect of beta-adrenoceptor blockade on thermoregulation during prolonged exercise

The effect of clinically used equipotent doses of nonselective (beta 1/beta 2; propranolol) and selective (beta 1; atenolol) beta-adrenoceptor blockers on thermoregulation was studied during prolonged exercise in the heat. Oral propranolol (160 mg/day), atenolol (100 mg/day) or matching placebo were taken for 6 days each by 11 healthy young adult caucasian males. Subjects participated in 2 h of block-stepping at a work rate of 54 W in an environmental chamber with a temperature of 33.2 +/- 0.3 degree C dry bulb and 31.7 /+- 0.3 degree C wet bulb, 2 h after ingestion of the final dose of each drug. Both active agents produced similar marked (P less than 0.001) increases in subjective perception of effort, the mechanism of which was not immediately evident from changes in serum electrolytes, blood glucose, blood lactate, or ventilatory parameters. Propranolol did, however, cause a greater rise in serum K+ than placebo (P less than 0.02) and atenolol (P = NS) after exercise. Although rectal and mean skin temperatures were insignificantly altered by beta-adrenoceptor blockade, an increased total sweat production was noted with propranolol (P less than 0.01 vs. placebo) and to a lesser degree atenolol (P = NS vs. placebo) therapy. Analysis of the time course of sweat production showed the propranolol-mediated enhancement of sweating to ensue largely during the initial hour of block-stepping and to be transient in nature. The scientific and clinical implications of this observation will be dependent upon the precise underlying mechanism, a factor not identified by the present study.     

Epinephrine is unessential for stimulation of liver glycogenolysis during exercise

To determine the role of adrenal medullary hormones in controlling the rate of liver glycogenolysis during exercise, adrenodemedullated (ADM) and sham-operated (SO) rats were run on a rodent treadmill at 21 m/min up a 15% grade for 0, 30, or 60 min. Rats were anesthetized by intravenous injection of pentobarbital sodium, and liver, muscle, and blood were collected and frozen. Liver glycogen decreased at similar rates in ADM and SO rats. Hepatic adenosine 3',5'-cyclic monophosphate (cAMP), plasma glucagon, and plasma free fatty acids increased to the same extent in both ADM and SO rats. The adrenodemedullation caused a reduction in glycogenolysis in the fast-twitch white region of the quadriceps, soleus, and lateral gastrocnemius during exercise. The normal exercise-induced increase in blood glucose and lactate and the decline in plasma insulin were not observed in the demedullated rats. During submaximal exercise the principal targets for epinephrine released from the adrenal medulla appear to be pancreatic beta-cells and skeletal muscle and not the liver.     

Effect of maternal exercise on fetal liver glycogen late in gestation in the rat

To determine the effect of maternal exercise on fetal liver glycogen content, fed and fasted rats that were pregnant for 20.5 or 21.5 days were run on a rodent treadmill for 60 min at 12 m/min with a 0% grade or 16 m/min up a 10% grade. The rats were anesthetized by intravenous injection of pentobarbital sodium, and fetal and maternal liver and plasma samples were collected and frozen. Fetal liver glycogenolysis did not occur as a result of maternal exercise. Fetal blood levels of lactate increased 22-60%, but glucose, plasma glucagon, and insulin were unchanged during maternal exercise. Maternal liver glycogen decreased as a result of exercise in all groups of rats except the fasted 20.5-day-pregnant group. Plasma free fatty acids increased in all groups and blood lactate increased in fed (20.5 days) and fasted (21.5 days) pregnant rats. Maternal glucose, glucagon, and insulin values remained constant during exercise. The fetus appears to be well-protected from metabolic stress during moderate-intensity maternal exercise.     

Comparison of the antilipolytic effect of metoprolol,acebutolol, and propranolol in man.

Metoprolol and acebutolol, two supposedly cardioselective beta-adrenoceptor antagonists, were tested in 11 healthy men against propranolol, a non-selective drug, for their effect on plasma free fatty acid concentrations before and after insulin. The fasting concentrations of free fatty acid were significantly reduced after acebutolol and propranolol, and their return to normal after insulin was delayed. Metoprolol had no significant effect on free fatty acid levels either before or after insulin. Although both selective and non-selective beta-blocking drugs should be expected to delay the return of free fatty acid values to normal after insulin, in contrast to propranolol and acebutolol, metoprolol had no such effect. This suggests that metoprolol may not be as effective as the other two drugs in controlling lipid metabolism during long-term treatment with beta-adrenoceptor antagonists.     

Beta-adrenergic blockade alters whole-body leucine metabolism in humans

This study examined the effects of a nonselective beta-blocking agent on whole-body leucine metabolism in humans. Five normal, healthy subjects (4 male, 1 female) underwent a 6-h primed, constant-rate infusion of L-[1-13C]leucine after 5 days of twice daily oral use of 80 mg propranolol and a placebo. Leucine turnover was determined by tracer dilution and leucine oxidation by 13C enrichment of the expired CO2. Propranolol decreased the total daily energy expenditure from 1,945 +/- 177.5 to 1,619 +/- 92.5 kcal/day (P less than 0.05). A fasting associated decrease in blood glucose and an attenuated rise in free fatty acids and ketones were observed during beta-blockade. Propranolol also increased plasma leucine concentrations (73.1 +/- 8.7 to 103.4 +/- 7.3 mumol/l; P less than 0.05) and leucine oxidation (13.2 +/- 1.2 to 17.1 +/- 1.3 mumol.kg-1.h-1; P less than 0.05), although leucine turnover was not significantly altered (100.5 +/- 7.3 vs. 126.0 +/- 12.3 mumol.kg-1.h-1). In addition, the urinary urea nitrogen-to-creatinine ratio was greater during propranolol administration (0.24 +/- 0.04 vs. 0.34 +/- 0.02 mol/g; P less than 0.05). These data suggest that the beta-adrenergic system plays a role in the modulation of whole-body leucine metabolism in humans. Whether these changes are the result of a direct effect on skeletal muscle or an indirect effect mediated by altering the fuel supply to skeletal muscle cannot be discriminated by the present study.     

Beta-blockers: once or three times a day?

In a double-blind, crossover trial 16 hypertensive patients were treated, in random order, with placebo, metoprolol 300 mg in a single daily dose, or metoprolol 300 mg/day in three doses. Both therapeutic regimens produced detectable plasma metoprolol concentrations and appreciable beta-blockade, estimated from exercise tachycardia, throughout the day. Fluctuations throughout the day in plasma drug concentrations and degree of beta-blockade were insignificant on the thrice-daily regimen, but they varied considerably on the single-dose regimen. Both therapeutic regimens also significantly lowered blood pressure throughout the day. Although the thrice-daily regimen again tended to produce a stronger and less fluctuating hypotensive action, the differences in hypotensive effect between the two regimens were not statistically significant. A single-dose of 300 mg of metoprolol can therefore be recommended if the only aim is to reduce blood pressure but not if a steady degree of beta-blockade is needed.     

The effect of beta-adrenergic blockade on leg blood flow with repeated maximal contractions of the triceps surae muscle group in man

The effect of beta-adrenergic blockade on torque output and leg blood flow was examined in seven healthy young men during repeated maximal isometric voluntary contractions of the triceps surae muscle group. Exercise was performed in either a bent- or straight-leg position during each of four drug treatments: placebo, propranolol, metoprolol, oxprenolol. Contractions were sustained for 5 s with 5 s relaxation for a total of 10 min followed by a 10-min recovery. Leg blood flow was measured during the 5 s relaxation separating contractions using strain gauge plethysmography. Torque output decreased during the 10-min contractions with no differences between the four drug treatments. Leg blood flow was lower with beta-blockade during the initial stages of exercise and recovery in the bent-leg position but no differences were observed after 3 min exercise or recovery. Leg blood flow in the straight-leg position was not different between any of the four drug treatments, but it was significantly less than in bent-leg exercise. The lower blood flows during the initial stages of exercise in the beta-blocked conditions probably reflect a slowing of the central cardiovascular response because of beta 1-receptor blockade of the heart rather than on the beta 2-receptors effects on peripheral vascular resistance. It is concluded that local vasodilator substances released from the working muscle may play a more important role than beta 2-receptor stimulation of smooth muscle in skeletal muscle resistance vessels in regulating local muscle blood flow during maximal exercise of the triceps surae muscle group.     

Gender differences in the regulation of amino acid metabolism.

Exercising men, compared with women, have a greater increase in leucine oxidation but not lysine rate of appearance. The cause for this sexual dimorphism is unknown; however, an inhibition of beta-adrenoreceptor activity has previously been shown to mediate amino acid metabolism (Lamont LS, McCullough AJ, and Kalhan SC. Am J Physiol Endocrinol Metab 268: E910-E916, 1995; Lamont LS, Patel DG, and Kalhan SC. J Appl Physiol 67: 221-225, 1989). This study was a gender comparison of leucine and lysine kinetics during a beta-adrenoreceptor blockade (beta1,beta2-blockade) and a placebo control by using a double-blind crossover protocol. Subjects exercised at 50% of their trial-specific maximal O2 consumption (1 h) after 7 days of dietary control. During exercise with beta-blockade, men had an increased nonprotein respiratory exchange ratio (P < 0.001), whereas women had an increased circulation of free fatty acids (P < 0.001). The genders also displayed distinct differences in exercise amino acid kinetics. The men, but not the women, increased leucine oxidation (P < 0.005) and lysine rate of appearance (P < 0.009) when exercising during beta-adrenergic blockade. This study indicates that during beta-blockade, exercising men increase their need for amino acids (and carbohydrate) to fuel energy needs, whereas women increase their mobilization of fat, thereby requiring less alternative fuels such as carbohydrate and amino acids. Gender-specific fuel preferences during exercise are regulated by beta-adrenergic-receptor activity. Substrate availability during exercise appears to modulate the amino acid oxidation differences between genders.     

Effect of beta-adrenergic blockade on lactate turnover in exercising dogs

Dogs with indwelling catheters in the jugular vein and in the carotid artery ran on the treadmill (slope: 15%, speed: 133 m/min). Lactate turnover and glucose turnover were measured using [U-14C]lactate and [3-3H]glucose as tracers, according to the primed constant-rate infusion method. In addition, the participation of plasma glucose in lactate production (Ra-L) was measured with [U-14C]glucose. Propranolol was given either (A) before exercise (250 micrograms/kg, iv) or (B) in form of a primed infusion administered to the dog running at a steady rate. Measurements of plasma propranolol concentration showed that in type A experiments plasma propranolol fell in 45 min below the lower limit of the complete beta-blockade. In the first 15 min of work Ra-L rose rapidly; then it fell below that of the control (exercise) values. During steady exercise, the elevated Ra-L was decreased by propranolol infusion close to resting values. beta-Blockade doubled the response of glucose production, utilization, and metabolic clearance rate to exercise. In exercising dogs approximately 40-50% of Ra-L arises from plasma glucose. This value was increased by the blockade to 85-90%. It is concluded that glycogenolysis in the working muscle has a dual control: 1) an intracellular control operating at the beginning of exercise, and 2) a hormonal control involving epinephrine and the beta-adrenergic receptors.     

Influence of alpha or beta adrenergic antagonists on catecholamine dependent metabolic effects in pigs

In 4 Piétrain-pigs and 4 crossbred (Duroc X Landrace) pigs (32-47 kg body weight; b.w.) the effect of an intravenous injection of epinephrine (80 micrograms/kg b.w.) or isoprenaline (55 micrograms/kg b.w.) was investigated during a continuous infusion of 0.9% NaCl-solution (1 ml/min and pig), propranolol or phentolamine (priming dose 100 micrograms/kg b.w. and thereafter 2 micrograms/kg and min over 45 min) on the plasma concentration of glucose, lactate, free fatty acids (FFS) and free over 45 min) on the plasma concentration of glucose, lactate, free fatty acids (FFS) and free glycerol. Furthermore the effect of a continuous infusion of the blocking agents alone was examined in the 4 crossbred animals. Lipolysis was stimulated via beta-adrenergic receptors and was inhibited through an alpha-adrenergic mediated effect in pigs. The lean Piétrain-pigs showed a significant higher response than the crossbred pigs. The catecholamine induced increase in plasma glucose and lactate was equal in both breeds. The rise of glucose concentration resulted from an alpha- and beta-adrenergic component, with the alpha-adrenergic effect dominating. Compared to isoprenaline, the higher increase in plasma lactate after adrenaline injection is attributed to clinical reactions.     

Effects of isotonic and isometric exercises with mist sauna bathing on cardiovascular,thermoregulatory, and metabolic functions

To clarify the effects of isometric and isotonic exercise during mist sauna bathing on the cardiovascular function, thermoregulatory function, and metabolism, six healthy young men (22?±?1 years old, height 173?±?4 cm, weight 65.0?±?5.0 kg) were exposed to a mist sauna for 10 min at a temperature of 40 °C, and relative humidity of 100 % while performing or not performing ～30 W of isometric or isotonic exercise. The effect of the exercise was assessed by measuring tympanic temperature, heart rate, systolic and diastolic blood pressure, chest sweat rate, chest skin blood flow, and plasma catecholamine and cortisol, glucose, lactate, and free fatty acid levels. Repeated measures ANOVA showed no significant differences in blood pressure, skin blood flow, sweat rate, and total amount of sweating. Tympanic temperature increased more during isotonic exercise, and heart rate increase was more marked during isotonic exercise. The changes in lactate indicated that fatigue was not very great during isometric exercise. The glucose level indicated greater energy expenditure during isometric exercise. The free fatty acid and catecholamine levels indicated that isometric exercise did not result in very great energy expenditure and stress, respectively. The results for isotonic exercise of a decrease in lactate level and an increase in plasma free fatty acid level indicated that fatigue and energy expenditure were rather large while the perceived stress was comparatively low. We concluded that isotonic exercise may be a more desirable form of exercise during mist sauna bathing given the changes in glucose and free fatty acid levels.     

Control of glycogen metabolism by gluconeogenic and ketogenic substrates in isolated hepatocytes from fed rats.

1. This study was conducted to examine the effects of gluconeogenic and ketogenic substrates on the activities of the glycogen-metabolizing enzymes and on glycogenolysis in isolated hepatocytes from fed rats. 2. Gluconeogenic substrates like fructose, dihydroxyacetone or lactate turned out to stimulate the glucose-induced activation of glycogen synthase and this effect may be linked, to some extent, to the increase of the cellular glucose 6-phosphate concentration. 3. The effect of fructose was accompanied by the onset of glycogen synthesis. 4. Energetic substrates like fatty acids were also potent activators of glycogen synthase, especially in the presence of glucose. 5. When fatty acids were added alone or together with a physiological concentration of glucose, they induced or potentiated the inhibition of glycogen phosphorylase-a. 6. This inhibitory effect was mediated by a decrease of lactate release. 7. The stimulatory effect of amino acids on glycogen synthase seemed to be direct, non mediated by an inhibition of the phosphorylase-a activity although hepatic glycogenolysis markedly decreased. 8. Moreover, the amino acid action could be linked to their capacities to induce cell swelling and/or to limit proteolysis.     

Substrate mobilization and hormonal changes in rainbow trout (Oncorhynchus mykiss,L.) and common carp (Cyprinus carpio,L.) during deep hypoxia and subsequent recovery

Common carp (at 20°C) and rainbow trout (at 15°C) were fitted with an indwelling cannula in the dorsal aorta. The fish were exposed to a controlled decline of waterpO₂ followed by 90 min deep hypoxia at 0.3 kPa (carp) or 4.8 kPa (trout). Thereafter, normoxic recovery was monitored in both species for 48 h. At regular intervals blood samples were analysed for glucose, lactate, free fatty acids, adrenaline, noradrenaline and cortisol. The oxygen restriction was maximal in both species and resulted in a significant increase of plasma lactate levels. In carp, adrenaline, noradrenaline and cortisol levels increased to 2, 50, and 753 ng·ml^-1 respectively during anoxia, whereas in trout these hormones increased to 12, 8 and 735 ng·ml^-1 respectively during hypoxia. In hypoxic trout, the plasma levels of glucose (3 mol·l^-1) were increased modestly whereas levels of free fatty acids (0.25 mmol·l^-1) were decreased to 0.15 mmol·l^-1. In carp, however, a marked and prolonged hyperglycaemia (from 5 to 10 mmol·l^-1) and a significant continuous depression of plasma levels of free fatty acids (from 0.4 to 0.2 mmol·l^-1) were observed indicating a difference in metabolic organization. It is suggested that hyperglycaemia is likely to be the result of hepatic glycogenolysis, stimulated by circulating catecholamines and a stimulation of gluconeogenesis by cortisol during recovery. The mechanism for the decline of plasma levels of free fatty acids is most probably a reduction of lipolytic activity, which appears to be an adaptation to hypoxia.     

Tocopherol mobilization during dynamic exercise after beta-adrenergic blockade.

This study addresses the question of whether tocopherol mobilization during exercise could be explained by a lipolysis effect. Nine healthy male subjects were submitted to dynamic exercise of graded intensity (45, 60, 75% VO2max) on a cycle ergometer after ingestion of either a placebo or 40 mg propranolol as beta-blocker. Plasma tocopherol concentration increased toward a peak value reached during or at the end of exercise. The magnitude of this increase did not differ in the two experimental conditions while plasma free fatty acids concentration was lowered under beta-adrenergic blockade by propranolol. From these results, we conclude that tocopherol mobilization during dynamic exercise does not depend on lipolysis.     

Thermoregulation during prolonged exercise in heat: alterations with beta-adrenergic blockade

Thermoregulation and cardiovascular drift were studied under conditions of prolonged exercise in a warm environment (dry bulb temperature 31.7 +/- 0.3 degrees C, rh 44.7 +/- 4.7%) during beta-adrenergic blockade. Fourteen subjects performed 90-min rides on a cycle ergometer at a work rate equivalent to 40% of their control maximal O2 uptake under each of three treatments provided in a randomized double-blind manner: atenolol (100 mg/day), propranolol (160 mg/day), and a placebo. Exercise during the propranolol trial resulted in significantly higher forearm vascular resistance values and significantly lower forearm blood flows (FBF) compared with the placebo trial. However, the significantly lower FBF during propranolol did not significantly alter the rectal temperature (Tre) response to prolonged exercise. In addition, both beta-blockers produced lower FBF for any given Tre, suggesting that beta-adrenergic blockade affects FBF through nonthermal factors. The slight differences in Tre, despite the large differences in FBF between the various treatments, are apparently the result of an enhanced sweat loss and a lower mean skin temperature during exercise with beta-blockade. The uncoupling of FBF and sweat loss provides evidence of independent regulation. The reduction in FBF at any given Tre was concomitant to lower blood pressure values during beta-blockade and suggests that baroreflexes provide significant input to the control of skin blood flow when both pressure and temperature maintenance are simultaneously challenged.