title: S-nitrosothiol modulation of tolerance to glyceryl trinitrate in bovine isolated coronary artery.
abstract: The aim of the study was to ascertain whether induction of tolerance to glyceryl trinitrate (GTN) was modified by nitrosothiols. Vasodilator responses to GTN and to two nitrosothiols, namely S-nitroso-N-acetylpenicillamine (SNAP) and S-nitroso-N-acetylcaptopril (SNOCAP) were measured in bovine coronary artery rings constricted with the thromboxane mimetic agent U46619. Pre-exposure of vessels to SNAP (10 microM) for 1 h resulted in cross-tolerance to GTN comparable with tolerance induced by GTN (1.0 microM). Tolerance was increased after pre-exposure to both agents. SNAP alone in lower concentrations (0.01, 0.1 and 1.0 microM) did not produce cross tolerance to GTN, but in combination with GTN (1.0 microM) caused a small but significant decrease in tolerance to GTN. This attenuating effect of SNAP on GTN tolerance was reproduced by SNOCAP (0.01 microM). We conclude that the nitrosothiols exert a biphasic effect on induction of tolerance to GTN.
authors.affiliation: Cardiology Unit, Queen Elizabeth Hospital, University of Adelaide, Woodville, Australia.
authors.forename: C L
authors.initials: CL
authors.lastname: Zhang
authors.forename: I S
authors.initials: IS
authors.lastname: De la Lande
authors.forename: I
authors.initials: I
authors.lastname: Stafford
authors.forename: J D
authors.initials: JD
authors.lastname: Horowitz
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D002216:Captopril / Q000031:analogs & derivatives* / Q000494:pharmacology; D002417:Cattle; D003331:Coronary Vessels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D066298:In Vitro Techniques; D005996:Nitroglycerin / Q000494:pharmacology*; D009603:Nitroso Compounds / Q000494:pharmacology*; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D009603:Nitroso Compounds; D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C060039:S-nitrosocaptopril; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D026423:S-Nitroso-N-Acetylpenicillamine; D002216:Captopril; D005996:Nitroglycerin; D010396:Penicillamine