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 (O2-) to generate peroxynitrite which at physiological pH gives rise to peroxynitrous acid than rapidly decomposes to hydroxyl radical (.OH) and nitrogen dioxide, .OH relaxes isolated aorta. It was hypothesized that Ach-induced vascular relaxation is mediated by .OH derived from interaction of NO and O2-. 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 O2- [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. DMTU, 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 O2- and NO. is the mediator of Ach-induced vascular relaxation. Thus while EDRF is NO. its mechanism of action involves .OH.
Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
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Prasad
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Bharadwaj
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000378:metabolism*; D066298:In Vitro Techniques; D008353:Mannitol / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits; D013482:Superoxide Dismutase / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D016166:Free Radical Scavengers; D017665:Hydroxyl Radical; D008353:Mannitol; C038983:1,3-dimethylthiourea; D013482:Superoxide Dismutase; D013890:Thiourea; D000109:Acetylcholine; D005905:Glyburide; D009638:Norepinephrine