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

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Abstract
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 (EC 50 =7.77×10 −8 versus 2.68×10 −8 mol/L, P P −8 versus 7.77×10 −8 mol/L, P 2 /thromboxane A 2 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.