Differential control of heart rate and sympathetic nerve activity during dynamic exercise. Insight from intraneural recordings in humans.

We used microelectrode recordings of muscle sympathetic nerve activity (MSNA) from the peroneal nerve in the leg during arm exercise in conscious humans to test the concept that central command and muscle afferent reflexes produce mass sympathetic discharge at the onset of exercise. Nonischemic rhythmic handgrip and mild arm cycling produced graded increases in heart rate and arterial pressure but did not increase MSNA, whereas ischemic handgrip and moderate arm cycling dramatically increased MSNA. There was a slow onset and offset of the MSNA responses, which suggested metaboreceptor mediation. When forearm ischemia was continued after ischemic handgrip, MSNA remained elevated (muscle chemoreflex stimulation) but heart rate returned to control (elimination of central command). The major new conclusions are that: the onset of dynamic exercise does not produce mass, uniform sympathetic discharge in humans, and muscle chemoreflexes and central command appear to produce differential effects on sympathetic and parasympathetic responses.

Estimated aortic stiffness is independently associated with cardiac baroreflex sensitivity in humans: role of ageing and habitual endurance exercise.

We hypothesised that differences in cardiac baroreflex sensitivity (BRS) would be independently associated with aortic stiffness and augmentation index (AI), clinical biomarkers of cardiovascular disease risk, among young sedentary and middle-aged/older sedentary and endurance-trained adults. A total of 36 healthy middle-aged/older (age 55-76 years, n=22 sedentary and n=14 endurance-trained) and 5 young sedentary (age 18-31 years) adults were included in a cross-sectional study. A subset of the middle-aged/older sedentary adults (n=12) completed an 8-week-aerobic exercise intervention. Invasive brachial artery blood pressure waveforms were used to compute spontaneous cardiac BRS (via sequence technique), estimated aortic pulse wave velocity (PWV) and AI (AI, via brachial-aortic transfer function and wave separation analysis). In the cross-sectional study, cardiac BRS was 71% lower in older compared with young sedentary adults (P<0.05), but only 40% lower in older adults who performed habitual endurance exercise (P=0.03). In a regression model that included age, sex, resting heart rate, mean arterial pressure (MAP), body mass index and maximal exercise oxygen uptake, estimated aortic PWV (ß±s.e.=-5.76±2.01, P=0.01) was the strongest predictor of BRS (model R(2)=0.59, P<0.001). The 8-week-exercise intervention improved BRS by 38% (P=0.04) and this change in BRS was associated with improved aortic PWV (r=-0.65, P=0.044, adjusted for changes in MAP). Age- and endurance-exercise-related differences in cardiac BRS are independently associated with corresponding alterations in aortic PWV among healthy adults, consistent with a mechanistic link between variations in the sensitivity of the baroreflex and aortic stiffness with age and exercise.

Central arterial compliance is associated with age- and habitual exercise-related differences in cardiovagal baroreflex sensitivity.

Background- Cardiovagal baroreflex sensitivity (BRS) declines with age but is favorably modulated by habitual aerobic exercise. We tested the hypothesis that compliance (transducing capacity) of an elastic artery in which baroreceptors are located is associated with these age-exercise interactions. Methods and Results- Nine young (28+/-1 years old) and 9 older (65+/-1) sedentary and 10 young (27+/-1) and 9 older (63+/-2) endurance-trained healthy men were studied. Cardiovagal BRS was assessed conventionally (R-R interval-systolic blood pressure [SBP] relation) by the Oxford technique. Because of age-associated increases in central arterial stiffness, cardiovagal BRS was expressed with both peripheral (Finapres) and central (applanation tonometry) SBP values. The change in carotid artery end-systolic lumen diameter (ultrasonography) per unit increase in SBP and the slope of the R-R interval-carotid artery diameter relation also were determined. Cardiovagal BRS declined with age in both sedentary ( approximately 65%) and endurance-trained ( approximately 40%) men but was higher in endurance-trained than sedentary older men regardless of the SBP values used (all P<0.05). Changes in carotid artery lumen diameter per unit increase in SBP mirrored these differences in cardiovagal BRS (all P<0.05). Thus, R-R interval prolongation per unit increase in carotid artery diameter was not different among the groups (P>0.70). Conclusions- These results demonstrate that age- and habitual exercise-related differences in cardiovagal BRS are associated with corresponding differences in carotid artery compliance among healthy men.

Limb blood flow and vascular conductance are reduced with age in healthy humans: relation to elevations in sympathetic nerve activity and declines in oxygen demand.

BACKGROUND: We tested the hypothesis that basal (resting) limb blood flow and vascular conductance are reduced with age in adult humans and that these changes are related to elevations in sympathetic vasoconstrictor nerve activity and reductions in limb oxygen demand. METHODS AND RESULTS: Sixteen young (28+/-1 years; mean+/-SEM) and 15 older (63+/-1 years) healthy normotensive adult men were studied. Diastolic blood pressure and body fat were higher (P<0.005) in the older men, but there were no other age-related differences in subject characteristics. Femoral artery blood flow (Doppler ultrasound) was 26% lower in the older men (P<0.005), despite similar levels of cardiac output (systemic arterial blood flow) in the 2 groups. Femoral artery vascular conductance was 32% lower and femoral vascular resistance was 45% higher in the older men (P<0. 005). Muscle sympathetic nerve activity (peroneal microneurography) was 74% higher in the older men (P<0.001) and correlated with femoral artery blood flow (r=-0.55, P<0.005), vascular conductance (r=-0.65, P<0.001), and vascular resistance (r=0.61, P<0.001). The age-related differences in femoral hemodynamics were no longer significant after correction for the influence of muscle sympathetic nerve activity. There were no significant age-group differences in leg tissue mass (by dual-energy x-ray absorptiometry), but estimated leg oxygen consumption was 15% lower in the older men (P<0.001). Femoral artery blood flow was directly related to estimated leg oxygen consumption (r=0.78, P<0.001). The age-group differences in femoral artery blood flow were no longer significant after correction for estimated leg oxygen consumption by ANCOVA. CONCLUSIONS: (1) Basal whole-leg arterial blood flow and vascular conductance are reduced with age in healthy adult men; (2) these changes are associated with elevations in sympathetic vasoconstrictor nerve activity; and (3) the lower whole-limb blood flow is related to a lower oxygen demand that is independent of tissue mass.

Aging, habitual exercise, and dynamic arterial compliance.

BACKGROUND: A reduction in compliance of the large-sized cardiothoracic (central) arteries is an independent risk factor for the development of cardiovascular disease with advancing age. METHODS AND RESULTS: We determined the role of habitual exercise on the age-related decrease in central arterial compliance by using both cross-sectional and interventional approaches. First, we studied 151 healthy men aged 18 to 77 years: 54 were sedentary, 45 were recreationally active, and 53 were endurance exercise-trained. Central arterial compliance (simultaneous B-mode ultrasound and arterial applanation tonometry on the common carotid artery) was lower (P:<0.05) in middle-aged and older men than in young men in all 3 groups. There were no significant differences between sedentary and recreationally active men at any age. However, arterial compliance in the endurance-trained middle-aged and older men was 20% to 35% higher than in the 2 less active groups (P:<0.01). As such, age-related differences in central arterial compliance were smaller in the endurance-trained men than in the sedentary and recreationally active men. Second, we studied 20 middle-aged and older (53+/-2 years) sedentary healthy men before and after a 3-month aerobic exercise intervention (primarily walking). Regular exercise increased central arterial compliance (P:<0.01) to levels similar to those of the middle-aged and older endurance-trained men. These effects were independent of changes in body mass, adiposity, arterial blood pressure, or maximal oxygen consumption. CONCLUSIONS: Regular aerobic-endurance exercise attenuates age-related reductions in central arterial compliance and restores levels in previously sedentary healthy middle-aged and older men. This may be one mechanism by which habitual exercise lowers the risk of cardiovascular disease in this population.

Regular aerobic exercise prevents and restores age-related declines in endothelium-dependent vasodilation in healthy men.

BACKGROUND: In sedentary humans endothelium-dependent vasodilation is impaired with advancing age contributing to their increased cardiovascular risk, whereas endurance-trained adults demonstrate lower age-related risk. We determined the influence of regular aerobic exercise on the age-related decline in endothelium-dependent vasodilation. METHODS AND RESULTS: In a cross-sectional study, 68 healthy men 22 to 35 or 50 to 76 years of age who were either sedentary or endurance exercise-trained were studied. Forearm blood flow (FBF) responses to intra-arterial infusions of acetylcholine and sodium nitroprusside were measured by strain-gauge plethysmography. Among the sedentary men, the maximum FBF response to acetylcholine was 25% lower in the middle aged and older compared with the young group (P:<0.01). In contrast, there was no age-related difference in the vasodilatory response to acetylcholine among the endurance-trained men. FBF at the highest acetylcholine dose was almost identical in the middle aged and older (17.3+/-1.3 mL/100 mL tissue per minute) and young (17.7+/-1.4 mL/100 mL tissue per minute) endurance-trained groups. There were no differences in the FBF responses to sodium nitroprusside among the sedentary and endurance- trained groups. In an exercise intervention study, 13 previously sedentary middle aged and older healthy men completed a 3-month, home-based aerobic exercise intervention (primarily walking). After the exercise intervention, acetylcholine-mediated vasodilation increased approximately 30% (P:<0.01) to levels similar to those in young adults and middle aged and older endurance-trained men. CONCLUSIONS: Our results indicate that regular aerobic exercise can prevent the age-associated loss in endothelium-dependent vasodilation and restore levels in previously sedentary middle aged and older healthy men. This may represent an important mechanism by which regular aerobic exercise lowers the risk of cardiovascular disease in this population.

Altered autonomic support of arterial blood pressure with age in healthy men.

BACKGROUND: Primary aging is associated with changes in the autonomic nervous system (ANS), but the functional significance of these changes for systemic circulatory control of arterial blood pressure (BP) is unknown. We tested the hypothesis that ANS support of BP is altered in healthy older humans. METHODS AND RESULTS: A total of 23 young (aged 24+/-1 years; systolic/diastolic BP, 126+/-2/66+/-1 mm Hg) and 16 older (aged 65+/-1 years; systolic/diastolic BP, 125+/-3/62+/-2 mm Hg) healthy men were studied before and during ganglionic blockade (intravenous trimethaphan). The reduction in mean BP (radial artery catheter) with trimethaphan was almost twice as great in the older men (-33+/-2 versus -19+/-2 mm Hg; -40% versus -22% of baseline; P<0.01) due to a lack of increase in heart rate (3+/-2 versus 25+/-2 bpm; P<0.001) and cardiac output (-0.42+/-0.19 versus 1.01+/-0.26 L/min; P<0.001); the decreases in systemic vascular resistance were not different. The absence of tachycardia in the older men was associated with reduced baseline heart rate variability (HRV, P<0.05); the change in heart rate with trimethaphan correlated with the standard deviation of the R-R intervals (HRV(SD R-R interval); r=0.57, P<0.001). Among individual subjects (pooled groups), the reductions in mean BP with trimethaphan were most strongly related to measures of sympathetic activity (r=0.58 to 0.67, P<0.005), change in mean BP with intravenous phenylephrine (r=0.57, P<0.001), and HRV(SD R-R interval) (r=-0.40, P<0.01). CONCLUSIONS: ANS support of BP is altered with age in healthy men due to less cardiac vagal inhibition of heart rate and cardiac output. Basal sympathetic activity and alpha-adrenergic vascular sensitivity are also key physiological correlates of ANS support of BP in healthy men.

Age-predicted maximal heart rate revisited.

OBJECTIVES: We sought to determine a generalized equation for predicting maximal heart rate (HRmax) in healthy adults. BACKGROUND: The age-predicted HRmax equation (i.e., 220 - age) is commonly used as a basis for prescribing exercise programs, as a criterion for achieving maximal exertion and as a clinical guide during diagnostic exercise testing. Despite its importance and widespread use, the validity of the HRmax equation has never been established in a sample that included a sufficient number of older adults. METHODS: First, a meta-analytic approach was used to collect group mean HRmax values from 351 studies involving 492 groups and 18,712 subjects. Subsequently, the new equation was cross-validated in a well-controlled, laboratory-based study in which HRmax was measured in 514 healthy subjects. RESULTS: In the meta-analysis, HRmax was strongly related to age (r = -0.90), using the equation of 208 - 0.7 x age. The regression equation obtained in the laboratory-based study (209 - 0.7 x age) was virtually identical to that obtained from the meta-analysis. The regression line was not different between men and women, nor was it influenced by wide variations in habitual physical activity levels. CONCLUSIONS: 1) A regression equation to predict HRmax is 208 - 0.7 x age in healthy adults. 2) HRmax is predicted, to a large extent, by age alone and is independent of gender and habitual physical activity status. Our findings suggest that the currently used equation underestimates HRmax in older adults. This would have the effect of underestimating the true level of physical stress imposed during exercise testing and the appropriate intensity of prescribed exercise programs.

Blood pressure reductions with exercise and sodium restriction in postmenopausal women with elevated systolic pressure: role of arterial stiffness.

OBJECTIVES: This study determined the relative efficacy of aerobic exercise (daily walking) and moderate dietary sodium restriction (sodium intake <100 mmol/day) for reducing systolic blood pressure (SBP) and pulse pressure (PP) in postmenopausal women with elevated initial levels, and the potential role of reductions in large artery stiffness in these changes. BACKGROUND: Lifestyle behaviors are recommended for lowering blood pressure (BP) in adults with elevated baseline levels, but there is little information as to the relative efficacy of different interventions or the mechanisms underlying their potential beneficial effects. METHODS: After baseline measurements and random assignment, 35 nonmedicated healthy postmenopausal women with SBP between 130 and 159 mm Hg completed three months of either aerobic (walking) exercise (n = 18; 62 +/- 9 years, mean +/- SD) or moderate dietary sodium restriction (SR) (n = 17; 65 +/- 10 years, mean +/- SD). RESULTS: Body mass and composition, plasma volume, and fasting concentrations of metabolic coronary risk factors did not differ between the groups at baseline or change with intervention. Systolic BP and PP at rest decreased with both exercise and SR (p < 0.05); however, the reductions were three- to fourfold greater with SR (p < 0.05). Sodium restriction, but not exercise, also reduced 24-h SBP and PP (p < 0.05). Aortic pulse wave velocity (PWV) and carotid augmentation index were reduced only with SR (p < 0.05). Changes in SBP and PP at rest and over 24 h correlated with the corresponding changes in aortic PWV (r = 0.53 to 0.61, p < 0.01). CONCLUSIONS: Moderate SR lowers SBP and PP in postmenopausal women with elevated baseline levels more than does daily walking. The greater blood pressure reductions with SR may be mediated in part by a decrease in the stiffness of the large elastic arteries.

Carotid artery wall hypertrophy with age is related to local systolic blood pressure in healthy men.

Carotid artery intima-media thickness (IMT) increases with advancing age in humans. The underlying mechanism of this increase is unknown, but data from animal studies suggest that a chronic increase in local distending pressure can act as a stimulus. To test this hypothesis, we studied a total of 129 healthy normotensive, nonobese, nonsmoking men aged 18 to 77 years. Brachial systolic blood pressure (SBP) was unchanged, but carotid SBP increased progressively with age (P<0.05). Carotid IMT and the ratio of carotid IMT to lumen (ultrasonography) increased progressively with age (P<0.05). Carotid IMT was approximately 50% greater in the older compared with the young men. Carotid SBP was positively related to carotid IMT (r=0.55, P<0.001). After carotid SBP was taken into account (ANCOVA), the age-related difference in carotid IMT was no longer statistically significant (P=0.22). We conclude that carotid IMT increases with age in healthy men in the absence of elevations in peripheral SBP. Carotid SBP increases progressively with advancing age in this population and is significantly related to the corresponding carotid wall hypertrophy. These results support the hypothesis that chronic increases in local distending pressure may be an important mechanism in the wall thickening that occurs with human aging in central elastic arteries.

Sympathetic neural adjustments to stress in physically trained and untrained humans.

The purpose of this study was to determine if the state of physical training influences sympathetic neural activation during acute stress in humans. We recorded muscle sympathetic nerve activity (microneurography of the peroneal nerve), arterial blood pressure, and heart rate in 12 highly trained, endurance athletes (25 +/- 1 years, mean +/- SEM) and 12 untrained subjects (27 +/- 1 years) before (supine rest control) and during: 1) lower body negative pressure at -5, -10, -15, and -20 mm Hg (orthostatic stress); 2) isometric handgrip at 30% of maximum (exercise stress); and 3) hand immersion in ice water, that is, the cold pressor test (thermal stress). Body weight was not different in the two groups, but the athletes had a lower body fat content (8.9 +/- 1.3% versus 16.1 +/- 2.0%, p less than 0.05). During supine rest, muscle sympathetic nerve burst frequency (24 +/- 3 versus 24 +/- 2 bursts/min, athletes versus untrained subjects) and burst incidence (36 +/- 3 versus 44 +/- 4 bursts/100 heart beats) and arterial blood pressure were not different in the two groups, but heart rate was lower in the athletes (54 +/- 2 versus 67 +/- 3 beats/min, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of regular exercise on 24-hour arterial pressure in older hypertensive humans.

The experimental goals were to determine if regular low-intensity aerobic exercise reduces 24-hour arterial blood pressure in middle-aged and older (aged 50 years or older) humans with mild diastolic (90-105 mm Hg) essential hypertension and, if so, whether this is accurately reflected by changes in casual recordings made at rest. Fourteen subjects walked 3-4 days/wk for 6 months, with 10 exercising an additional 6 months; 12 other subjects served as nonexercising controls. In the exercising subjects, maximal oxygen consumption increased 7-14% (p less than 0.05) with little or no change in body weight or fat. Conventional casual readings of systolic, mean, and diastolic arterial pressure at rest were lower (5-10 mm Hg, p less than 0.05) in all body positions after 6 months of exercise and changed little thereafter. Casual recordings made during additional circulatory measurements showed 6-month decreases of only half this magnitude and were specific to a particular blood pressure phase and body position; however, all changes were significant after 12 months of exercise. The reductions in arterial pressure at rest were associated with decreases in heart rate (p less than 0.05) and cardiac output (p less than 0.05). Ambulatory-determined 24-hour arterial pressure was unchanged after 6 months of exercise, but mean levels were slightly lower (4 mm Hg, p less than 0.05) after 12 months due to reductions in daytime (7 mm Hg, p less than 0.05) and nighttime (4 mm Hg, NS) systolic pressure; diastolic pressure was unchanged throughout the year of training. In the controls, conventionally recorded casual blood pressure levels were lower after 6 months (p less than 0.05), but no other changes were observed in any other variable over the 12 months of study. We conclude 1) regular low-intensity aerobic exercise at best produces only small reductions in 24-hour levels of arterial pressure in middle-aged and older humans with mild (diastolic) essential hypertension and 2) training-associated changes in casually determined blood pressure at rest are dependent on the measurement conditions and, most importantly, do not necessarily reflect the magnitude or even the direction of changes in arterial pressure throughout an entire day.

Postexercise hypotension. Key features, mechanisms, and clinical significance.

Recent investigations have demonstrated that there is a sustained reduction in arterial blood pressure after a single bout of exercise, ie, postexercise hypotension (PEH). The purpose of this discussion is to integrate the available information on this topic and to review studies using sustained stimulation of somatic afferents in experimental rats as a model to study the role of somatic afferents in PEH. PEH occurs in response to several types of large-muscle dynamic exercise (ie, walking, running, leg cycling, and swimming) at submaximal intensities greater than 40% of peak aerobic capacity and exercise durations generally between 20 and 60 minutes. PEH is observed in both normotensive and hypertensive humans and in spontaneously hypertensive rats but is generally greater in magnitude in hypertensive subjects. The maximal exercise-induced reductions in systolic and diastolic arterial blood pressures have been on average 18 to 20 and 7 to 9 mm Hg, respectively, in hypertensive humans and 8 to 10 and 3 to 5 mm Hg, respectively, in normotensive humans. PEH has been reported to persist for 2 to 4 hours under laboratory conditions. Whether PEH is sustained for a prolonged period of time under free-living conditions remains controversial, although the results of one study indicate that PEH can persist for up to 13 hours. Possible mechanisms involved in mediating postexercise and poststimulation reductions in arterial blood pressure include decreased stroke volume and cardiac output; reductions in limb vascular resistance, total peripheral resistance, and muscle sympathetic nerve discharge; group III somatic afferent activation; altered baroreceptor reflex circulatory control; reduced vascular responsiveness to alpha-adrenergic receptor-mediated stimulation; and activation of endogenous opioid and serotonergic systems. It appears that the magnitude of PEH in hypertensive subjects is clinically significant; however, more investigation is required to determine if the duration is sufficient under real-life conditions to contribute to the reduction in blood pressure observed with chronic exercise conditioning.

Augmented cardiopulmonary and integrative sympathetic baroreflexes but attenuated peripheral vasoconstriction with age.

Based on observations of smaller increases in limb vascular resistance during acute incremental hypovolemia in older adults, cardiopulmonary and integrative (combined cardiopulmonary and arterial) baroreflex control of sympatho-circulatory function is thought to be impaired with aging in humans. We tested this hypothesis directly by making intraneural measurements of skeletal muscle sympathetic nerve activity (MSNA; peroneal microneurography) in groups of young (23+/-1 years; n=11) and older (64+/-1 years; n=12) healthy adult men during progressive hypovolemia produced by graded (-5 to -40 mm Hg) lower body negative pressure (LBNP). Baseline levels of MSNA and arterial blood pressure were higher and heart rate was lower in the older subjects (P<0.05). Lower levels of LBNP (-5 to -20 mm Hg) did not affect arterial blood pressure or heart rate in either group; systolic and pulse pressures declined during higher levels of LBNP (-30 and -40 mm Hg) but only in the young subjects (P<0.05). Graded LBNP evoked progressive, linear reductions in peripheral venous pressure (PVP) and increases in MSNA, plasma norepinephrine concentration (PNE), and forearm vascular resistance (FVR) in both groups (all P<0.05). DeltaMSNA/ deltaPVP was approximately 150% greater in the older versus young men during both lower and higher levels of hypovolemia (P<0.01); however, deltaFVR/deltaPVP was approximately 50% smaller in the older men (P<0.05). There was no difference in the MSNA-PNE relation with age, but deltaFVR/deltaMSNA was approximately 65% to 70% smaller in the older subjects (P<0.05). Our findings indicate that cardiopulmonary and integrative baroreflex control of central sympathetic outflow during hypovolemia is augmented, not impaired, with age in healthy humans. However, the reflex-mediated increases in limb vascular resistance during hypovolemia are smaller in older adults because of attenuated vasoconstrictor responsiveness to sympathetic stimulation.

Age and gender influence muscle sympathetic nerve activity at rest in healthy humans.

Muscle sympathetic nerve activity at rest increases with age in humans. The respective influences of the aging process per se and gender on this increase and whether age and gender effects on muscle sympathetic nerve activity can be identified with plasma norepinephrine concentrations, however, have not been established. To examine these issues, nine young women (aged 24 +/- 1 years; mean +/- SEM), eight young men (aged 26 +/- 1 years), seven older women (aged 63 +/- 1 years), and eight older men (aged 66 +/- 1 years) were studied. All were healthy, normotensive (blood pressure < 140/90 mm Hg), nonobese (< 20% above ideal weight), unmedicated, nonsmokers engaged in minimal to recreational levels of chronic physical activity. Arterial blood pressure (manual sphygmomanometry, brachial artery), heart rate, muscle sympathetic nerve activity (peroneal microneurography), and antecubital venous plasma norepinephrine concentrations (radioenzymatic assay) were determined during quiet supine resting conditions. Body weight was higher in men, but there were no age-related differences, whereas estimated body fat (sum of skinfolds) was higher in women and in the older groups (p < 0.05). Estimated daily energy expenditure, arterial blood pressure, and heart rate were not different among the groups. Both muscle sympathetic nerve activity burst frequency and burst incidence at rest were progressively higher in the young women, young men, older women, and older men (10 +/- 1 versus 18 +/- 2 versus 25 +/- 3 versus 39 +/- 5 bursts/min and 16 +/- 1 versus 30 +/- 4 versus 40 +/- 3 versus 61 +/- 6 bursts/100 heartbeats, respectively; all p < 0.05 versus each other).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of the cold pressor test on muscle sympathetic nerve activity in humans.

The purpose of this study was to determine the effects of the cold pressor test on sympathetic outflow with direct measurements of nerve traffic in conscious humans and to test the strength of correlation between sympathetic nerve discharge and the changes in arterial pressure, heart rate, and plasma norepinephrine. In 25 healthy subjects, arterial pressure, heart rate, and muscle sympathetic nerve activity were measured with microelectrodes inserted percutaneously into a peroneal muscle nerve fascicle in the leg during immersion of the hand in ice water for 2 minutes. Arterial pressure rose steadily during the first and second minutes of the cold pressor test. Muscle sympathetic activity (burst frequency X amplitude) did not increase in the first 30 seconds of the test but increased from 230 +/- 27 to 386 +/- 52 units (mean +/- SE, p less than 0.05) by the end of the first minute of the test and to 574 +/- 73 (p less than 0.01) during the second minute. In contrast, heart rate increased maximally during the first 30 seconds of the cold pressor test and returned to control during the second minute. The increases in heart rate were abolished by beta-adrenergic blockade. The increases in muscle sympathetic activity during the cold pressor test were correlated with the increases in both mean arterial pressure (r = 0.86, p less than 0.01) and peripheral venous norepinephrine (r = 0.72, p less than 0.05); however, large changes in nerve traffic were associated with small changes in plasma norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

Arterial baroreceptor reflex modulation of sympathetic-cardiovascular adjustments to heat stress.

The purpose of this study was to determine if the arterial baroreceptor reflexes modulate the sympathocirculatory responses to acute heat stress. To address this, arterial pressure, heart rate, mesenteric and renal blood flow velocity (Doppler flow probes), arterial plasma norepinephrine, and colonic temperature were measured before and during whole body heating (42 degrees C ambient temperature) in groups of conscious, unrestrained rats with (sham) or without (sinoaortic deafferentation) intact arterial baroreceptor reflexes. Heating was stopped when a colonic temperature of 41 degrees C was attained. Baseline levels of arterial pressure were similar in the two groups, whereas heart rate was elevated in deafferented versus sham-operated rats (p less than 0.01). The increases above baseline for both arterial pressure (73 +/- 4 vs. 27 +/- 2 mm Hg) and heart rate (127 +/- 10 vs. 33 +/- 5 beats/min) were threefold to fourfold greater at the end of heating in the deafferented versus the sham group (p less than 0.01). Declines in mesenteric and renal blood flow were similar in the two groups during heating; however, deafferented rats had greater increases in both mesenteric and renal vascular resistance (p less than 0.05). Plasma norepinephrine was elevated at baseline in deafferented versus sham rats and increased in both groups during heating (p less than 0.01). The magnitude of the increase in plasma norepinephrine from baseline to 41 degrees C was fivefold greater in the deafferented versus the sham rats (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Tonic sympathetic support of metabolic rate is attenuated with age, sedentary lifestyle, and female sex in healthy adults.

We recently demonstrated in young adult humans that the sympathetic nervous system contributes to the control of resting metabolic rate via tonic beta-adrenergic receptor stimulation. In the present follow-up study we determined the respective effects of age, habitual exercise status, and sex on this regulatory mechanism. Resting metabolic rate (ventilated hood, indirect calorimetry) was determined in 55 healthy sedentary or endurance exercise-trained adults, aged 18-35 or 60-75 yr (29 men and 26 women), before (baseline) and during the infusion of either a nonselective beta-adrenergic receptor antagonist (propranolol) or saline (control). Relative to baseline values, during beta-adrenergic receptor antagonism resting metabolic rate adjusted for fat-free mass was reduced to a lesser extent in older (mean +/- SE, -130 +/- 46 kJ/d) compared with young (-297 +/- 46) adults, sedentary (-151 +/- 50) compared with endurance exercise-trained (-268 +/- 46) adults, and women (-105 +/- 33) compared with men (-318 +/- 50; all P < 0.01). Reductions in resting metabolic rate during beta-adrenergic receptor antagonism were positively related to higher baseline resting metabolic rate and plasma catecholamine concentrations and negatively related to adiposity (all P < 0.05). Resting metabolic rate was unchanged in response to saline control in all groups. These results provide experimental support for the hypothesis that aging, sedentary living, and female sex are associated with attenuated sympathetic nervous system support of resting metabolic rate in healthy adult humans.

Regular exercise and the age-related decline in resting metabolic rate in women.

A low resting metabolic rate (RMR) is a risk factor for future weight gain. We tested the hypothesis that the age-related decline in RMR in sedentary women is not observed in women who exercise regularly. Sixty-five healthy, weight-stable women, aged 21-35 or 50-72 yr, were studied: 12 premenopausal and 15 postmenopausal sedentary women, 13 premenopausal and 15 postmenopausal distance runners, and 10 endurance-trained postmenopausal swimmers. RMR was measured by indirect calorimetry (ventilated hood system) after an overnight fast, and values were adjusted for fat mass and fat-free mass (RMRadj). The RMRadj was approximately 10% lower in the postmenopausal vs. premenopausal sedentary women (52 +/- 2 vs. 57 +/- 2 Cal/h; P < 0.002). In contrast, RMRadj was not significantly different in the premenopausal (59 +/- 2 Cal/h) and postmenopausal (57 +/- 1 Cal/h) distance runners. The postmenopausal swimmers had a RMRadj (57 +/- 2 Cal/h) identical to that of the postmenopausal runners, suggesting a generalized influence of the endurance exercise-trained state in postmenopausal women. Group differences in RMRadj were not associated with differences in total energy intake or composition or with plasma concentrations of norepinephrine, T3, or T4. However, maximal oxygen consumption (aerobic fitness) accounted for 35% of the individual variance in RMRadj in the overall population (r = 0.59; P < 0.001). Our results are consistent with the concept that the age-related decline in RMR in sedentary women is not observed in women who regularly perform endurance exercise. The elevated level of RMR observed in middle-aged and older exercising women may play a role in their lower levels of body weight and fatness compared to those in sedentary women.

Postexercise hypotension and sympathoinhibition in borderline hypertensive men.

To determine if there would be a decrease in blood pressure after exercise in patients with borderline hypertension and if this decrease would be accompanied by a decrease in sympathetic nerve activity to muscle, we recorded multifiber postganglionic muscle sympathetic activity from the peroneal nerve at rest in nine men with borderline hypertension (age 25 +/- 1 years, mean +/- SEM) before and 60 minutes after 45 minutes of submaximal treadmill exercise. In addition, responses to a cold pressor test, handgrip, and the Valsalva maneuver were recorded before and after exercise. Four subjects were also studied before and after "sham" exercise. Sham exercise had no effect on blood pressure or sympathetic nerve activity whereas resting systolic blood pressure was lower after treadmill exercise in seven subjects (from 136 +/- 4 before to 123 +/- 2 mm Hg 60 minutes after exercise; p less than 0.01). Sixty minutes after exercise, sympathetic nerve activity was lower in all seven subjects (from 19 +/- 2 to 11 +/- 2 bursts/min, p less than 0.015; or from 27 +/- 3 to 14 +/- 2 bursts/100 heartbeats, p less than 0.005) but was slightly increased in the two subjects without postexercise hypotension. Heart rate and pressor and sympathoneural responses to the cold pressor test, handgrip, and the Valsalva maneuver were not altered by prior exercise. When nitroprusside was infused in five subjects to produce a reduction in systolic blood pressure similar to that seen 60 minutes after exercise, this drug increased sympathetic discharge from 37 +/- 6 to 57 +/- 4 bursts/100 heartbeats (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)