Aging Is Associated With Reduced Prostacyclin-Mediated Dilation in the Human Forearm

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Abstract
Aging is associated with reduced endothelial function. There is indirect evidence for reduced prostacyclin (PGI 2 )-mediated vasodilation with aging, but it is unknown whether this is because of reduced dilation to PGI 2 or altered production. In addition, the contribution of endothelial NO to PGI 2 -mediated dilation is unknown. Using plethysmography to determine forearm blood flow, we studied the effect of PGI 2 in 10 older (61 to 73 years) and 10 younger (19 to 45 years) subjects using 3 escalating intra-arterial doses of PGI 2 (epoprostenol). PGI 2 was also administered after NO synthase inhibition with N G -monomethyl- l -arginine acetate. The percent of change in forearm vascular conductance (mean±SEM) from baseline after PGI 2 was significantly lower ( P =0.002) in the aging individuals (52±11%, 164±23%, and 221±27% versus 115±20%, 249±19%, and 370±35%). In addition, the group-by-dose interaction was also significant ( P =0.018). After NO synthase inhibition, the dose-response curve to PGI 2 was blunted in the young subjects but unchanged in the older subjects; the difference between the groups was no longer significant. Our data suggest that the reduced dilator effects of PGI 2 in older individuals are attributable to a reduction in the contribution of endothelial-derived NO versus alterations in the direct effects of PGI 2 on vascular smooth muscle.