Relaxing effect of nicorandil (N-2-(hydroxyethyl)-nicotinamide nitrate), a new anti-angina agent, on the isolated vascular smooth muscle.
To define the mode of the vasorelaxing action of nicorandil as compared to nitroglycerin, the effects of the agent on the contractile response to various stimulations in rabbit aorta, cat coronary arteries and rabbit basilar arteries were evaluated. Nicorandil had a greater relaxing effect on the maximum response to norepinephrine (NE) than on the potassium (K+) response on all vascular smooth muscles used. In coronary and basilar arteries, however, the inhibitory action of nitroglycerin was not different on the response to both agonists. In coronary and basilar arteries the maximum inhibition of the NE response by nicorandil was greater than that by nitroglycerin. Nicorandil (10(-5) M) but not phentolamine (10(-5) M) inhibited the PGF2 alpha-induced contraction of the aorta. Either nicorandil or nitroglycerin suppressed the response of the aorta to the transmural stimulation. In a Ca2+-free medium containing K+ (40 mM), nicorandil decreased the response to excess Ca2+ in all preparations whereas, nifedipine (10(-6)-10(-5) M) abolished it. Nitroglycerin, however, had no effect on the Ca2+-induced contraction on basilar arteries. In a Ca2+-free medium, the residual NE-induced contraction was inhibited by nicorandil or nitroglycerin but not by nifedipine . The combined treatment with nicorandil and nitroglycerin caused a stronger suppression of residual NE response that that of a single treatment with either agent suggesting the different site of action for the two agents. These results suggest that the mode of vasorelaxing action of nicorandil may be due to the alteration (inhibition) of Ca2+ kinetics in the cell.
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001488:Basilar Artery / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology; D002415:Cats; D003331:Coronary Vessels / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil; D009543:Nifedipine / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D009536:Niacinamide; D020108:Nicorandil; D011189:Potassium Chloride; D005996:Nitroglycerin; D009543:Nifedipine; D002118:Calcium; D009638:Norepinephrine