Effects of H2O2 on membrane potential of smooth muscle cells in rabbit mesenteric resistance artery

The effects of H2O2 on the membrane potential of smooth muscle cells of rabbit mesenteric resistance arteries were investigated. H2O2 (3-30 muM) concentration-dependently hyperpolarized the membrane; this was inhibited by catalase but not by superoxide dismutase or the hydroxyl-radical scavenger dimethylthiourea. The cyclooxygenase inhibitor diclofenac partly inhibited the responses; the subsequent addition of the 5-lipoxygenase inhibitor 2-(12-hydroxydodeca-5,10-diynyl)-3,5,6-trimethyl-p-benzoquinone (AA-861) (but not the cytochrome P-450 inhibitor 17-octadecynoic acid) further attenuated H2O2-induced hyperpolarizations. The sarcolemmal ATP-sensitive K+ (K-ATP) channel inhibitor 1-{5-[2-(5-chloro-o-anisamido)ethyl]-2-methoxyphenylsulfonyl}-3-methylthiourea, sodium salt (HMR-1098), blocked the H2O2-induced hyperpolarization in the absence and presence of diclofenac. H2O2 increased the production of prostaglandin E-2 and prostacyclin (estimated from its stable metabolite 6-keto-prostaglandin F-1alpha), both of which produce a HMR-1098-sensitive hyperpolarization in the smooth muscle cells. It is concluded that, in smooth muscle cells of rabbit mesenteric artery, H2O2 increases the synthesis of vasodilator prostaglandins and possibly 5-lipoxygenase products, which produce a hyperpolarization by activating sarcolemmal K-ATP channels. (C) 2003 Elsevier Science B.V All rights reserved.