Older age in healthy men was associated with a 30% lower forearm blood flow response to acetylcholine (P<0.01), while responses to bradykinin, substance P, and isoproterenol were preserved.
Cross-Sectional (n=63)
Is the age-related reduction in endothelium-dependent vasodilatation specific to acetylcholine or a general endothelial cell vasomotor abnormality in healthy men?
Age-related impairment in endothelium-dependent vasodilatation in healthy men is specific to acetylcholine and does not universally affect other endothelial agonists like bradykinin or substance P.
Effect estimate: 30% lower
Absolute Event Rate: 12.3% vs 17.1%
p-value: p=< 0.01
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) x min(-1)) and older men (4.0 +/- 0.2 ml (100 ml tissue)(-1) x min(-1)). The increase in FBF at the highest dose of acetylcholine was approximately 30 % lower (P < 0.01) in the older (from 4.0 +/- 0.2 to 12.3 +/- 0.7 ml (100 ml tissue)(-1) x min(-1)) compared with young men (from 3.9 +/- 0.2 to 17.1 +/- 1.5 ml (100 ml tissue)(-1) x 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) x min(-1)), substance P (15.1 +/- 0.8 vs. 16.8 +/- 0.7 ml (100 ml tissue)(-1) x min(-1)) and isoproterenol (17.5 +/- 0.9 vs. 17.5 +/- 0.9 ml (100 ml tissue)(-1) x 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 response 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.
DeSouza et al. (Mon,) conducted a cross-sectional in Healthy (n=63). Older age (50-76 years) vs. Young age (23-35 years) was evaluated on Forearm blood flow response to the highest dose of acetylcholine (30% lower, p=< 0.01). Older age in healthy men was associated with a 30% lower forearm blood flow response to acetylcholine (P<0.01), while responses to bradykinin, substance P, and isoproterenol were preserved.
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