Hydroxyl radical - A mediator of acetylcholine induced vascular relaxation

It is well known that acetylcholine (Ach)-induced vasodilation is mediated through the release of the endothelium-derived relaxing factor (EDRF), nitric oxide (NO .). It has been suggested that NO interacts with superoxide anion (O-2(-)) to generate peroxynitrite which at physiological pH gives rise to peroxynitrous acid that rapidly decomposes to hydroxyl radical (. OH) and nitrogen dioxide, . OH relaxes isolated aorta. II was hypothesized that Ach-induced vascular relaxation is mediated by . OH derived from interaction of NO and O-2(-). To test this hypothesis we investigated the effect of Ach on norepinephrine (NE)-precontracted isolated rabbit aortic preparations in the absence or presence of scavengers of O-2(-) [superoxide dismutase (SOD)] and of . OH [dimethylthiourea (DMTU) or mannitol]. . OH and Ach produced relaxation of NE-precontracted preparations in a concentration-dependent manner. Relaxation produced by OH generating system was prevented by mannitol, a . OH scavenger suggesting that relaxation is due to . OH. SOD, DR/ITU, mannitol or combination of SOD and DMTU markedly reduced the Ach-induced relaxation, Glyburide (an ATP-sensitive K+ channel blocker) was ineffective in blocking the Ach-induced remaining relaxation in the presence of SOD and DMTU, These results suggest that . OH formed from interaction of O-2(-) and NO . is the mediator of Ach-induced vascular relaxation, Thus while EDRF is NO ., its mechanism of action involves . OH. (C) 1996 Academic Press Limited