PMID: 2484698Jan 1, 1989Paper

Tolerance and cross-tolerance between SIN-1 and nitric oxide in bovine coronary arteries

Journal of Cardiovascular Pharmacology
W R Kukovetz, S Holzmann

Abstract

The molecular mechanism of tolerance development to nitrovasodilators, most prominent with nitroglycerin, associated with desensitization of guanylate cyclase is still unclear. Nitric oxide (NO) appears to be the common denominator of this group of drugs that leads to guanylate cyclase activation, followed by increases in levels of cyclic GMP and relaxation. It was therefore decided to study whether NO itself, which causes some tolerance, interferes with the actions of (a) SIN-1 and sodium nitroprusside, both of which are thought to act directly by NO formation, which explains why they cause little tolerance; and (b) with the actions of nitroglycerin, which stimulates cyclic GMP formation only in the presence of cysteine and causes pronounced (large) tolerance. Experiments were performed in circular strips of isolated de-endothelialized bovine coronary artery by measuring isotonic changes in length and cyclic GMP determined by radioimmunoassay. When the strips were treated with submaximal effective concentrations of NO, some tolerance was observed, as shown by moderate attenuation of the rises in cyclic GMP, and a rightward shift of the dose-response curve of the relaxing effects by a dose factor of 10 (DF = 10). Exposure to ni...Continue Reading

Related Concepts

Related Feeds

Antianginal Drugs: Mechanisms of Action

Antianginal drugs, including nitrates, beta-blockers, and calcium channel blockers, are used in the treatment of angina pectoris. Here is the latest research on their use and their mechanism of action.

Related Papers

European Journal of Clinical Pharmacology
W R Kukovetz, S Holzmann
American Heart Journal
W R Kukovetz, S Holzmann
European Journal of Pharmacology
W R Kukovetz, S Holzmann
© 2022 Meta ULC. All rights reserved