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Ageing affects nitric oxide synthase, cyclooxygenase and oxidative stress enzymes expression differently in mesenteric resistance arteries

Abstract:

Our aim was to study the role of nitric oxide (NO) and arachidonic acid pathways in the α1-adrenoceptor-mediated vasoconstriction in mesenteric resistance arteries from 3-4 and 22 to 23-month-old Sprague-Dawley rats. The expression of NO synthase (NOS), cyclooxygenase (COX) isoforms, soluble guanylate cyclase, superoxide dismutase and the NAD(P)H oxidase subunits p22phox and p47phox were determined. The N G-nitro-L-arginine methyl ester, a non-selective NOS inhibitor, shifted to the left but indomethacin and NS 398, non-selective and selective COX-2 inhibitors, shifted to the right the concentration-response curve for the vasoconstriction by phenylephrine in both age groups. Ageing up-regulated endothelial NOS and p22phox expression but did not modify COX, soluble guanylate cyclase, superoxide dismutase and p47phox expression. These data suggest that the observed enhancement of eNOS protein expression could constitute a compensatory mechanism to counter-regulate a chronic loss of NO possibly through increased superoxide anion production from NAD(P)H oxidase induced by age. © 2005 Blackwell Publishing Ltd.