AGING PROGRESSIVELY IMPAIRS ENDOTHELIUM-DEPENDENT VASODILATION IN FOREARM RESISTANCE VESSELS OF HUMANS

Studies in experimental models suggest that endothelium-derived nitric oxide is reduced with aging, and this circumstance may be relevant to atherogenesis. The aim of this study was to determine whether increas ing age resulted in altered endothelium-dependent vasodilation in the forearm resistance vessels of healthy humans. Forearm blood flow was m easured in 119 healthy subjects, aged 19 to 69 years, by venous occlus ion plethysmography. Brachial artery infusions of methacholine chlorid e (0.03 to 10.0 mu g/min) were used to assess endothelium-dependent va sodilation and of sodium nitroprusside (0.03 to 10.0 mu g/min) to asse ss endothelium-independent vasodilation. The slope of the dose-blood f low response relation was calculated in each subject for each drug. Un ivariate and multiple stepwise regression analyses were used to relate vascular reactivity to selected variables, including age, lipids, and blood pressure. Endothelium-dependent vasodila tion was progressively impaired with increasing age, assessed as a reduction in slope from 2 .25+/-0.16 to 0.34+/-0.11 (mL/100 mL tissue per minute)/(mu g/min) (P< .001). The decline in endothelium-dependent vasodilation was already e vident by the fourth decade (age 30 to 39 years). Endothelium-independ ent vasodilation did nut change with age. Age, total cholesterol, and low-density lipoprotein cholesterol were univariate predictors of endo thelium-dependent vasodilation. Age remained the most significant pred ictor of endothelium-dependent vasodilator responses by multiple stepw ise regression analysis. From these observations, it can be concluded that endothelium-dependent vasodilation declines steadily with increas ing age in healthy human subjects. Age is a strong univariate and mult ivariate predictor of endothelium-dependent vasodilation. This finding may be a marker for more widespread endothelial dysfunction.