Linda F. Shapiro

Regular Aerobic Exercise Prevents and Restores Age-Related Declines in Endothelium-Dependent Vasodilation in Healthy Men

BackgroundIn 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 ResultsIn 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 ≈30% (P <0.01) to levels similar to those in young adults and middle aged and older endurance-trained men. ConclusionsOur 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.

Evidence for agonist‐specific endothelial vasodilator dysfunction with ageing in healthy humans

Endothelium‐dependent vasodilatation declines with advancing age in humans independently of disease. The mechanisms responsible for this decline are not clear. We determined whether the age‐related reduction in endothelium‐dependent vasodilatation in response to acetylcholine reflects a specific agonist‐related defect or rather a more general endothelial cell vasomotor abnormality. Twenty‐two young (23‐35 years) and 41 older (50‐76 years) healthy men were studied. Forearm blood flow (FBF) responses to intra‐arterial infusions of acetylcholine, bradykinin, substance P, isoproterenol (isoprenaline) and sodium nitroprusside were measured by strain‐gauge plethysmography. There were no differences in resting FBF between the young (3.9 ± 0.2 ml (100 ml tissue)−1 min−1) and older men (4.0 ± 0.2 ml (100 ml tissue)−1 min−1). The increase in FBF at the highest dose of acetylcholine was ∼30 % lower (P < 0.01) in the older (from 4.0 ± 0.2 to 12.3 ± 0.7 ml (100 ml tissue)−1 min−1) compared with young men (from 3.9 ± 0.2 to 17.1 ± 1.5 ml (100 ml tissue)−1 min−1). In contrast to acetylcholine, the FBF responses to the other endothelial agonists were not impaired with age. The maximum increases in FBF in response to bradykinin (19.2 ± 1.0 vs. 20.2 ± 0.9 ml (100 ml tissue)−1 min−1), substance P (15.1 ± 0.8 vs. 16.8 ± 0.7 ml (100 ml tissue)−1 min−1) and isoproterenol (17.5 ± 0.9 vs. 17.5 ± 0.9 ml (100 ml tissue)−1 min−1) were not significantly different between the older and young subjects. There were no age‐related differences in the FBF responses to sodium nitroprusside. These results demonstrate that, although acetylcholine‐induced vasodilatation is impaired with age, forearm endothelial vasodilatation in reponse to bradykinin, substance P and isoproterenol are well preserved in healthy men. Moreover, these findings suggest that agonist‐stimulated endothelium‐dependent vasodilatation is not universally impaired with age.

Is autonomic support of arterial blood pressure related to habitual exercise status in healthy men

We determined if the tonic autonomic nervous system (ANS) contribution to arterial blood pressure (BP) maintenance in humans is related to habitual endurance exercise status. Twenty‐three healthy young (age 18–31 years) males, 11 endurance exercise‐trained and 12 untrained, were studied. Maximal oxygen consumption was higher (P < 0.001) and resting heart rate and body fatness were lower (P < 0.05) in the exercise‐trained men. Plasma noradrenaline concentrations and BP decreased from baseline levels in response to ganglionic blockade (intravenous trimethaphan) in both groups (all P < 0.001). The absolute (ΔmmHg: systolic =−35 ± 2 vs. −32 ± 4; diastolic =−13 ± 2 vs. −10 ± 2; mean =−21 ± 2 vs. −17 ± 3) and relative (Δ%: systolic =−35 ± 2 vs. −31 ± 3; diastolic =−26 ± 3 vs. −20 ± 3; mean =−31 ± 2 vs. −26 ± 3) decreases in BP were not significantly different between the endurance‐trained and untrained men. There were no significant group differences in the heart rate, stroke volume, cardiac output or systemic vascular resistance (conductance) responses to trimethaphan. Systemic vascular α‐adrenergic sensitivity (slope of the increase in mean BP with incremental phenylephrine infusion during ganglionic blockade) also did not differ in the two groups (endurance‐trained: 3.2 ± 0.5; untrained: 3.2 ± 0.7 mmHg (ng phenylephrine)−1 (ml plasma)−1). In the pooled sample, the decrease in mean BP during trimethaphan was related to baseline and changes in plasma noradrenaline concentrations (r= 0.58–0.65, P < 0.001) and α‐adrenergic sensitivity (r= 0.49, P < 0.02). Our results suggest that the endurance exercise‐trained state is not obviously associated with altered ANS support of BP in healthy young men. Basal sympathetic nervous system (SNS) activity and α‐adrenergic vascular sensitivity are significant physiological correlates of ANS support of BP in this population.

IS AUTONOMIC SUPPORT OF ARTERIAL BLOOD PRESSURE RELATED TO HABITUAL EXERCISE STATUS IN HEALTHY MEN

We determined if the tonic autonomic nervous system (ANS) contribution to arterial blood pressure (BP) maintenance in humans is related to habitual endurance exercise status. Twenty-three healthy young (age 18-31 years) males, 11 endurance exercise-trained and 12 untrained, were studied. Maximal oxygen consumption was higher (P < 0.001) and resting heart rate and body fatness were lower (P < 0.05) in the exercise-trained men. Plasma noradrenaline concentrations and BP decreased from baseline levels in response to ganglionic blockade (intravenous trimethaphan) in both groups (all P < 0.001). The absolute (Delta mmHg: systolic = -35 +/- 2 vs. -32 +/- 4; diastolic = -13 +/- 2 vs. -10 +/- 2; mean = -21 +/- 2 vs. -17 +/- 3) and relative (Delta%: systolic = -35 +/- 2 vs. -31 +/- 3; diastolic = -26 +/- 3 vs. -20 +/- 3; mean = -31 +/- 2 vs. -26 +/- 3) decreases in BP were not significantly different between the endurance-trained and untrained men. There were no significant group differences in the heart rate, stroke volume, cardiac output or systemic vascular resistance (conductance) responses to trimethaphan. Systemic vascular alpha-adrenergic sensitivity (slope of the increase in mean BP with incremental phenylephrine infusion during ganglionic blockade) also did not differ in the two groups (endurance-trained: 3.2 +/- 0.5; untrained: 3.2 +/- 0.7 mmHg (ng phenylephrine)(-1) (ml plasma)(-1)). In the pooled sample, the decrease in mean BP during trimethaphan was related to baseline and changes in plasma noradrenaline concentrations (r = 0.58-0.65, P < 0.001) and alpha-adrenergic sensitivity (r = 0.49, P < 0.02). Our results suggest that the endurance exercise-trained state is not obviously associated with altered ANS support of BP in healthy young men. Basal sympathetic nervous system (SNS) activity and alpha-adrenergic vascular sensitivity are significant physiological correlates of ANS support of BP in this population.