title: Peroxynitrite stimulates vascular smooth muscle cell cyclic GMP synthesis.
abstract: Peroxynitrite stimulated the synthesis of cyclic GMP by rat aortic smooth muscle in a time- and dose-dependent manner. Peak formation of cyclic GMP occurred at 1 min with 100 microM peroxynitrite and was inhibited by oxyhemoglobin. Peroxynitrite was less potent than nitric oxide in stimulating cyclic GMP synthesis. Peroxynitrite also enhanced endothelial-dependent cyclic GMP synthesis, via generation of a long-lived substance, which was prevented by inhibition of glutathione synthesis. These data show that peroxynitrite stimulates cyclic GMP synthesis, inferring production of low yields of nitric oxide or associated derivatives. Additionally, vascular exposure to peroxynitrite potentiates endothelial-dependent activation of guanylate cyclase.
authors.affiliation: Department of Anesthesiology, University of Alabama at Birmingham 35294, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Tarpey
authors.forename: J S
authors.initials: JS
authors.lastname: Beckman
authors.forename: H
authors.initials: H
authors.lastname: Ischiropoulos
authors.forename: J Z
authors.initials: JZ
authors.lastname: Gore
authors.forename: T A
authors.initials: TA
authors.lastname: Brock
mesh_terms: D000818:Animals; D001011:Aorta; D002417:Cattle; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000096:biosynthesis* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation; D005978:Glutathione / Q000096:biosynthesis; D006162:Guanylate Cyclase / Q000378:metabolism; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009566:Nitrates / Q000494:pharmacology*; D009569:Nitric Oxide / Q000494:pharmacology; D010108:Oxyhemoglobins / Q000494:pharmacology; D051381:Rats
chemical_list: D009566:Nitrates; D010108:Oxyhemoglobins; C039642:peroxynitric acid; D009569:Nitric Oxide; D006162:Guanylate Cyclase; D005978:Glutathione; D006152:Cyclic GMP