Effects of N-(2-hydroxyethyl)nicotinamide nitrate (SG-75) on methacholine-induced ECG changes in intact anesthetized rats.
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.
D000109:Acetylcholine / Q000494:pharmacology; D000758:Anesthesia; D000787:Angina Pectoris / Q000503:physiopathology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects; D008297:Male; D008688:Methacholine Compounds / Q000494:pharmacology*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil; D009566:Nitrates / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014665:Vasodilator Agents / Q000494:pharmacology*
D008688:Methacholine Compounds; D009566:Nitrates; D014665:Vasodilator Agents; D009536:Niacinamide; D020108:Nicorandil; D000109:Acetylcholine