Mechanisms of hydrogen peroxide-induced relaxation in rabbit mesenteric small artery

The effects of hydrogen peroxide were studied on isolated rabbit mesenteric small artery, rabbit superior mesenteric artery and mouse aorta were also studied as reference tissues. For mesenteric small artery, hydrogen peroxid e (1 to 100 muM) relaxed a norepinephrine stimulated artery in a concentrat ion-dependent manner. The relaxation was not significantly affected by remo val of the endothelium and was less pronounced in arteries contracted with high-KCl solution plus norepinephrine than in those contracted with norepin ephrine alone. The relaxation response to hydrogen peroxide was increased b y isobutylmethylxanthine and zaprinast, inhibited by diclofenac, methylene blue and dithiothreitol and unaffected by atropine, tetraethylammonium, sup eroxide dismutase, deferoxamine, dimethyl sulfoxide or the Rp stereoisomer of adenosine cyclic monophosphothioate. Hydrogen peroxide shifted concentra tion-contractile response curves for norepinephrine to the right and downwa rds. Norepinephrine and caffeine elicited a transient, phasic contraction o f the mesenteric small artery exposed for 0.5, 1 and 2 min to a Ca2+-free s olution. Hydrogen peroxide inhibited the norepinephrine-induced contraction , and to a lesser extent the caffeine-induced contraction, and verapamil di d not alter the contraction to norepinephrine. These pharmacological proper ties of hydrogen peroxide were similar to those of 8-bromo cGMP; 8-bromo cG MP inhibited more potently the norepinephrine-induced than the KCl-induced contraction and the contraction elicited by norepinephrine in Ca2+-free sol ution. The present results suggest that hydrogen peroxide induces endotheli um-independent relaxation of the rabbit mesenteric small artery precontract ed with norepinephrine. The effects of hydrogen peroxide may be at least in part mediated by cGMP and cyclooxygenase products in the vascular smooth m uscles now used. (C) 2001 Elsevier Science B.V. All rights reserved.