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(Hypertension. 2000;35:1242.)
© 2000 American Heart Association, Inc.

Scientific Contributions

Aging Increases PGHS-2–Dependent Vasoconstriction in Rat Mesenteric Arteries

Ken G. Stewart; Yunlong Zhang; Sandra T. Davidge

From the Departments of Obstetrics/Gynecology and Physiology, Perinatal Research Centre, University of Alberta, Edmonton, Canada.

Correspondence to Sandra T. Davidge, PhD, 232 Heritage Medical Research Centre, Perinatal Research Centre, University of Alberta, Edmonton, Canada, T6G 2S2. E-mail sandra.davidge{at}ualberta.ca

Abstract—During aging, the vascular endothelium changes functionally and morphologically. Although previous studies have shown that endothelium-derived eicosanoids increase vessel tone in aging, the precise mechanism(s) has not been fully determined. We hypothesized that aging would increase prostaglandin H synthase (PGHS)-dependent vasoconstriction as well as decrease nitric oxide–dependent relaxation. Mesenteric arteries from 3-month-old (n=9) and 12-month-old (n=14) female Sprague-Dawley rats were studied in a myograph system. Aging significantly blunted the endothelium-dependent relaxation response to methacholine compared with young rats (EC₅₀=7.77x10^-8 versus 2.68x10^-8 mol/L, P<0.05). Nitric oxide synthase inhibition reduced methacholine-induced relaxation in the young (P<0.05) but had no effect in the aging group. Specific inhibition of the PGHS-1 isoform did not significantly affect methacholine-mediated relaxation in the young or aged groups. However, PGHS-2 inhibition greatly enhanced relaxation to methacholine (1.59x10^-8 versus 7.77x10^-8 mol/L, P<0.01) in the aged group only, restoring vessel function to that of the young. In the aged group, inhibition of the prostaglandin H₂/thromboxane A₂ receptor enhanced methacholine-dependent relaxation similar to that of PGHS-2 inhibition. Moreover, arterial expression of PGHS-2 protein increased with age. In summary, nitric oxide–dependent modulation of vessel function decreased with age, PGHS-1 did not significantly affect vessel tone in either the young or aging group, and PGHS-2 greatly increased vasoconstriction in aging. Thus, we have identified enhanced PGHS-2–mediated vasoconstriction in aging and therefore suggest that inhibition of this isoform is potentially a new target for therapeutic intervention to improve vascular function.

Key Words: prostaglandins • vasculature • aging • nitric oxide • endothelium

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