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

Christopher A. DeSouza *†, Christopher M. Clevenger *, Jared J. Greiner *, Derek T. Smith *, Greta L. Hoetzer *, Linda F. Shapiro * and Brian L. Stauffer ‡

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.

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