Rapid tolerance to formation of authentic NO from nitroglycerin in vivo.
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.
Persson
M G
MG
Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
Agvald
P
P
Gustafsson
L E
LE
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
D009569:Nitric Oxide; D001120:Arginine; D005996:Nitroglycerin; D005978:Glutathione; D003545:Cysteine; D019331:NG-Nitroarginine Methyl Ester; D000111:Acetylcysteine