Aging is associated with endothelial dysfunction in the human forearm vasculature

OBJECTIVE: Our objective was to examine the role of the endothelium in maintaining vascular tone in the basal as well as in the contracted state during aging. DESIGN/PARTICIPANTS: Responses to brachial artery infusion of acetylcholine in presence and absence of N(G)-nitro-L-arginine methyl ester (L-NAME) and to angiotensin II were studied in 11 young and 12 old white subjects. MEASUREMENTS: Strain gauge plethysmography was used to measure forearm vascular resistance (FVR). The dose of acetylcholine at 50% maximal observed decrease in forearm vascular resistance (EC₅₀) was significantly higher (11.0 ± 1.59 vs 7.07 ± .65 μg/min, respectively; mean ± SEM; P < .05) and the FVR at maximal acetylcholine effect (Emax) remained greater (12.6 ± 1.75 vs 7.15 ± 1.25 mm Hg/100 mL tissue volume/min; P < .02) in old compared with young subjects. Acetylcholine effect was significantly reversed by concomitant administration of L-NAME, as indicated by the increase in EC₅₀ (old, 20.2 ± 3.69; young, 11.9 ± 1.68 μg/min). RESULTS: There was no age-related difference in sodium nitroprusside-induced decrease in FVR. The EC₅₀ and Emax for angiotensin II-mediated increase in FVR were 7.87 ± 1.15 and 8.36 ± 1.00 ng/min (EC₅₀) and 5.30 ± .67 vs 6.56 ± 1.25 mm Hg/100 mL tissue volume/min (Emax), and these were not different in old and young subjects, respectively. CONCLUSIONS: These data indicate that aging is associated with impaired endothelial- dependent vascular relaxation and that this is selective, with no age-related change in endothelial-independent vascular relaxation or angiotensin II-mediated vascular contraction.