title: Rapid tolerance to formation of authentic NO from nitroglycerin in vivo.
abstract: Direct evidence for in vivo NO formation from nitroglycerin (GTN) was obtained by measurements of exhaled nitric oxide in anaesthetized. Infusions of GTN (1-100 micrograms kg-1 min-1 i.v.) induced dose-dependent and biphasic increments in exhaled NO parallelled by reductions in systemic blood pressure. The NO detected during GTN infusion was unaffected by the nitric oxide synthase inhibitor L-NAME or acute i.v. administration of L-cysteine, N-acetyl-L-cysteine or glutathione. The present data demonstrate that NO is formed from GTN in vivo, and that tolerance in vivo is due to decreased formation of NO.
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
authors.forename: M G
authors.initials: MG
authors.lastname: Persson
authors.forename: P
authors.initials: P
authors.lastname: Agvald
authors.forename: L E
authors.initials: LE
authors.lastname: Gustafsson
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003545:Cysteine / Q000494:pharmacology; D004361:Drug Tolerance; D005978:Glutathione / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D007262:Infusions, Intravenous; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism*; D005996:Nitroglycerin / Q000378:metabolism* / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects; D011817:Rabbits
chemical_list: D009569:Nitric Oxide; D001120:Arginine; D005996:Nitroglycerin; D005978:Glutathione; D003545:Cysteine; D019331:NG-Nitroarginine Methyl Ester; D000111:Acetylcysteine