Inhibition of development of tolerance to nitroglycerin by preventive administration of N-acetylcysteine in rats.
The efficacy of N-acetylcysteine in reversing nitrate tolerance has been controversial. This study examined whether continuous administration of N-acetylcysteine, a sulfhydryl compound, can prevent the development of tolerance to nitroglycerin; its acute effects on developed tolerance were also assessed. Rats were treated with subcutaneous injections of 1) 100 mg/kg nitroglycerin, 2) 100 mg/kg nitroglycerin and 700 mg/kg N-acetylcysteine, 3 times a day for 3 days. The sensitivity to nitroglycerin was studied in aortic preparations. The degree of developed tolerance to nitroglycerin was partially inhibited by simultaneous injection of N-acetylcysteine. Subsequent in vitro preincubation of aortic strips with nitroglycerin (10(-5) M) reduced the subsequent nitroglycerin sensitivity of vessels from rats treated with nitroglycerin and N-acetylcysteine; sensitivity returned to the initial control level after in vitro preincubation with N-acetylcysteine. The nitroglycerin sensitivity of vessels from rats treated only with nitroglycerin, though, was not affected by in vitro preincubation with N-acetylcysteine. In conclusion, N-acetylcysteine is not effective in reversing the high degree of tolerance developed to nitroglycerin. However, continuous administration of N-acetylcysteine is effective in preventing the development of nitroglycerin tolerance.
Tsuneyoshi
H
H
Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Akatsuka
N
N
Ohno
M
M
Hara
K
K
Ochiai
M
M
Moroi
M
M
D000111:Acetylcysteine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004361:Drug Tolerance; D066298:In Vitro Techniques; D008297:Male; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014664:Vasodilation / Q000187:drug effects
D005996:Nitroglycerin; D000111:Acetylcysteine