Tolerance induction by transdermal glyceryl trinitrate in rats.
Mechanisms of mild glyceryl trinitrate tolerance in rats (transdermal application; 15 mg/day/2 days) were examined in isolated aortic rings contracted with phenylephrine. Tolerance to glyceryl trinitrate was comparable in both endothelium-intact and -denuded vessels; the maximum relaxation decreased to 70-80% and the EC50 increased 3-4-fold. There was minimal cross-tolerance to acetylcholine (1.7-fold increase in EC50) and none to sodium nitroprusside. The results suggest that mild tolerance to glyceryl trinitrate in rats is mediated by mechanisms which are predominantly endothelium-independent and which produce little activation of the cellular mechanism responsible for cross-tolerance.
De la Lande
I S
IS
Cardiology Unit, North Western Adelaide Health Service, The Queen Elizabeth Hospital, University of Adelaide, South Australia, Australia. ilande@tqehsmtp.tqeh.sa.gov.au
Stafford
I
I
Horowitz
J D
JD
D000109:Acetylcholine / Q000494:pharmacology; D000279:Administration, Cutaneous; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D066298:In Vitro Techniques; D008297:Male; D005996:Nitroglycerin / Q000008:administration & dosage* / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage*
D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; D005996:Nitroglycerin; D000109:Acetylcholine