Cellular mechanisms of action of therapeutic nitric oxide donors.

摘要: A survey of the available literature leads to conclusion that most probable mechanism by which nitrovasodilators act, is nitric oxide (NO) formation. This itself or formation a nitrosothiol (e.g. nitroscocysteine) activates guanylyl cyclase increases production cyclic guanosine monophosphate (cGMP). Endothelium-derived relaxing factor (EDRF), later turned out be form NO, relaxes smooth muscle stimulating cGMP formation[1]. The effect ofcGMP mediated cGMP-dependent protein kinase and causes reduction in intracellular concentration free Ca2+ ions cell. precise this not completely clear but sequestration into sarcoplasmatic reticulum seems play major role. In order identify nature endogenous stimulator cyclase, i.e. decide whether it radical we compared effects nitrosocysteine nitrosoglutathione on vascular relaxation levels isolated bovine circular strips activity vitro. Induction tolerance cross-tolerance between various NO donors was also investigated. Nitrosodium augmented relaxed slightly more powerfully than NO. three agents induced slight after repeated administration without affecting rises desensitizing cyclase. Pretreatment coronary with caused largely similar as did against nitroglycerin, SIN-1 sodium nitroprusside. similarities characterize its likely precursor, e.g. EDRF. Marked tolerance, seen associated densensitization whereas may (SIN-1, nitroprusside) (NO, nitrosocysteine, nitrosaglutathione) desensitization