Characterization of four different effects elicited by H2O2 in rat aorta

Four main vascular effects of hydrogen peroxide (H2O2) were studied in intact and rubbed aortic rings from WKY rats. In rings partially precontracted with phenylephrine: 1-30 mu M H2O2 induced an increase of tone, 100 mu M H2O2 produced a transient contraction followed by a fast-developing endothelium-in dependent relaxation, and 0.3 mM H2O2 induced a fast-developing relaxation followed by a slow-developing endothelium-in dependent relaxation. Superoxide dismutase (SOD) or dimethyl sulfoxide (DMSO)/manitol did not significantly modify the H2O2 effects, while catalase suppressed them. Indomethacin abolished the increase of tone elicited by H2O2 and revealed a small endothelium-dependent relaxation, which was suppressed by N-G-nitro-L-arginine (L-NA), high K+ or tetraethylammonium (TEA). TEA strongly inhibited the fast-developing relaxation while indomethacin, glybenclamide, 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), cafeic acid or eicosatdynoic acid (ETI) did not affect the relaxation. In rings precontracted with 70 mM KCI, 1-100 mu M H2O2 induced a small increase of tone and 0.3 mM a slow-developing relaxation. Catalase or Fe2+-EDTA/vitamin C suppressed the slow-developing relaxation while deferoxamine did not modify it. In rings partially precontracted with arachidonic acid, 1-30 PM H2O2, induced higher contractile effects than in rings partially precontracted with phenylephrine. H2O2 at 0.3 mM for one hour induced a persistent impairment on the reactivity of the rings and the release of lactate dehydrogenase. In summary, H2O2, produces: (1) contractions mediated by direct activation of cyclooxygenase; 2) endothelium-dependent relaxations related to activation of endothelial K channels and NO synthesis; 3) reversible endothelium-independent relaxations mediated by activation of smooth muscle K+ channels; and 4) irreversible endothelium-independent relaxations related to cellular damage, caused by H2O2 but not by hydroxyl radicals. (c) 2005 Elsevier Inc. All rights reserved.