Open AccessEffects of N-(2-hydroxyethyl)nicotinamide nitrate (SG-75) on methacholine-induced ecg changes in intact anesthetized rats.
Author(s) -
Junichiro Aono,
Michitaka Akima,
Kazushige Sakai
Publication year - 1981
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.31.823
Subject(s) - methacholine , papaverine , vasodilation , medicine , anesthesia , perfusion , vasoconstriction , nicotinamide , cardiology , chemistry , pharmacology , biochemistry , respiratory disease , lung , enzyme
The effects of a newly developed nicotinamide derivative, N-(2-hydroxyethyl)nicotinamide nitrate (SG-75, Nicorandil), were examined in an experimental model of angina pectoris, utilizing methacholine-induced ECG changes as main parameter in intact anesthetized rats. The right carotid artery was exposed and through it a special cannula was inserted to a point near the right and left coronary ostium. Such a device made it possible to inject drugs more selectively into the coronary artery. Single intra-aortic injections of 4 to 8 micrograms of methacholine caused a transient elevation of the ST segment and T wave of the electrocardiogram (ECG). SG-75 (3 mg/kg i.v. or 10 mg/kg p.o.) prevented these changes in the ECG, while a potent vasodilator, papaverine, failed to do so. In the isolated, donor-perfused rat heart, SG-75 (1-30 micrograms) injected into the coronary perfusion system caused dose-dependent vasodilation, while 0.1-0.8 micrograms acetylcholine as well as methacholine produced marked vasoconstriction. SG-75 (10 mg/kg) administered orally to the donor rat inhibited the coronary vasoconstriction produced by the cholinomimetic drugs, whereas papaverine (30 micrograms i.a.) failed to prevent it. The inhibitory effects of SG-75 on methacholine-induced ECG changes in intact rats seemed to be due to its spasmolytic action.