Oxyradicals as a mechanism of acetylcholine-induced vascular relaxation

Abstract

Acetylcholine (Ach)-induced vascular relaxation is accepted to be mediated by nitric oxide (NO·), endothelium-derived hyperpolarizing factor (EDHF), and prostaglandins released from endothelium. NO· activates guanylate cyclase which converts guanosine triphosphate to cyclic guanosine monophosphate (cGMP) that produces vascular relaxation. However there is some evidence which suggests that Ach-induced vascular relaxation may be mediated by hydroxyl radicals (·OH). NO· reacts rapidly with superoxide anion (O− 2) in a radical-radical coupled interaction to generate peroxynitrite anion which at physiological pH gets converted to peroxynitrous acid. Peroxynitrous acid is very unstable and rapidly decomposes to yield ·OH. There are numerous supporting evidences which suggest that Ach-induced vascular relaxation is mediated by ·OH. Ach and ·OH produce concentration-dependent vascular relaxation. Superoxide dismutase (SOD), a scavenger of O− 2, and mannitol and dimethylthiourea, scavengers of ·OH, reduce the Ach-induced vascular relaxation. NG monomethyl-L-arginine, an inhibitor of NO· synthase, inhibits endothelium-dependent vascular relaxation to Ach. ·OH also stimulates guanylate cyclase similar to NO·. ·OH-induced vascular relaxation may also be mediated by cyclooxygenase and EDHF. In conclusion, these data suggest that Ach-induced vascular relaxation may be mediated by ·OH generated from interaction of O− 2 and NO·.