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(Hypertension. 2009;53:973.)
© 2009 American Heart Association, Inc.

Original Articles

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

Wayne T. Nicholson; Brianna Vaa; Christiane Hesse; John H. Eisenach; Michael J. Joyner

From the Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester Minn. Current address (C.H.): Institute of Clinical Pharmacology, Bayer HealthCare AG, Wuppertal, Germany.

Correspondence to Wayne T. Nicholson, Department of Anesthesiology, College of Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905. E-mail nicholson.wayne{at}mayo.edu

Aging is associated with reduced endothelial function. There is indirect evidence for reduced prostacyclin (PGI₂)-mediated vasodilation with aging, but it is unknown whether this is because of reduced dilation to PGI₂ or altered production. In addition, the contribution of endothelial NO to PGI₂-mediated dilation is unknown. Using plethysmography to determine forearm blood flow, we studied the effect of PGI₂ in 10 older (61 to 73 years) and 10 younger (19 to 45 years) subjects using 3 escalating intra-arterial doses of PGI₂ (epoprostenol). PGI₂ 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 PGI₂ 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 PGI₂ 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 PGI₂ in older individuals are attributable to a reduction in the contribution of endothelial-derived NO versus alterations in the direct effects of PGI₂ on vascular smooth muscle.

Key Words: aging • prostaglandins • NO • blood flow

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