title: Modification of nitrovasodilator effects on vascular smooth muscle by exogenous GTP and guanosine.
abstract: The effects of exogenous guanosine 5'-triphosphate (GTP) and guanosine on nitroglycerin-, sodium nitrite- and SIN-1-induced guanosine 3',5'-cyclic monophosphate (cyclic GMP) accumulation and smooth muscle relaxation were studied using endothelium-denuded rat mesenteric artery rings precontracted with noradrenaline. Preincubation of contracted artery rings with GTP (100 microM) or guanosine (100 microM) before eliciting relaxations with nitrovasodilators significantly shifted the dose-response curves of nitrocompounds to the left and augmented the increases in cyclic GMP. GTP and guanosine alone also induced cyclic GMP accumulation in pre-contracted artery rings. These effects of GTP and guanosine on nitrovasodilator responses were not related to the preincubation period (0-30 min). The present results raise the possibility of a cell membrane site of action for GTP and guanosine, which mediates the activation of soluble guanylate cyclase and leads to increased nitrovasodilator-induced cyclic GMP accumulation and arterial smooth muscle relaxation.
authors.affiliation: Department of Biomedical Sciences, University of Tampere, Finland.
authors.forename: P
authors.initials: P
authors.lastname: Vuorinen
authors.forename: I
authors.initials: I
authors.lastname: Pörsti
authors.forename: T
authors.initials: T
authors.lastname: Metsä-Ketelä
authors.forename: V
authors.initials: V
authors.lastname: Manninen
authors.forename: H
authors.initials: H
authors.lastname: Vapaatalo
authors.forename: K E
authors.initials: KE
authors.lastname: Laustiola
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D006151:Guanosine / Q000494:pharmacology*; D006160:Guanosine Triphosphate / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D005996:Nitroglycerin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012977:Sodium Nitrite / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D006151:Guanosine; C002385:linsidomine; D006160:Guanosine Triphosphate; D008981:Molsidomine; D005996:Nitroglycerin; D006152:Cyclic GMP; D012977:Sodium Nitrite