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.

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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 24Ϯ1 years; systolic/diastolic BP, 126Ϯ2/66Ϯ1 mm Hg) and 16 older (aged 65Ϯ1 years; systolic/diastolic BP, 125Ϯ3/62Ϯ2 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 (Ϫ33Ϯ2 versus Ϫ19Ϯ2 mm Hg; Ϫ40% versus Ϫ22% of baseline; PϽ0.01) due to a lack of increase in heart rate (3Ϯ2 versus 25Ϯ2 bpm; PϽ0.001) and cardiac output (Ϫ0.42Ϯ0.19 versus 1.01Ϯ0.26 L/min; PϽ0.001); 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, PϽ0.05); the change in heart rate with trimethaphan correlated with the standard deviation of the R-R intervals (HRV SD R-R interval ; rϭ0.57, PϽ0.001). Among individual subjects (pooled groups), the reductions in mean BP with trimethaphan were most strongly related to measures of sympathetic activity (rϭ0.58 to 0.67, PϽ0.005), change in mean BP with intravenous phenylephrine (rϭ0.57, PϽ0.001), and HRV SD R-R interval (rϭϪ0.40, PϽ0.01). 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 ␣-adrenergic vascular sensitivity are also key physiological correlates of ANS support of BP in healthy men.

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.