Effects of N-(2-hydroxyethyl)nicotinamide nitrate (SG-75) on methacholine-induced ecg changes in intact anesthetized rats.

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Abstract
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 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, making it possible to inject drugs more selectively into the coronary artery. Single intra-aortic [i.a.] injections of 4-8 .mu.g of methacholine caused a transient ST and T wave elevation. SG-75 (3 mg/kg i.v. or 10 mg/kg orally) prevented these changes; a potent vasodilator, papaverine, did not. In the isolated, donor-perfused rat heart, SG-75 (1-30 .mu.g) infected into the coronary perfusion system caused dose-dependent vasodilation; 0.1-0.8 .mu.g acetylcholine and methacholine produced marked vasoconstriction. SG-75 (10 mg/kg orally) inhibited the coronary vasoconstriction produced by the cholinomimetic drugs; papaverine (30 .mu.g i.a.) did not. Evidently, the inhibitory effects of SG-75 on methacholine-induced ECG changes in intact rats were due to its spasmolytic action.