The mechanism of inhibitory effects of nicorandil, a new antianginal agent, on contractile responses to alpha 1- and alpha 2-adrenoceptor agonists in isolated vascular smooth muscles.
Effects of nicorandil on contractile responses to alpha 1-(methoxamine) and alpha 2-(clonidine and BHT-920) adrenoceptor agonists were examined in isolated rabbit aortae and femoral arteries. Nicorandil (10(-6) M and 10(-5) M) had greater inhibitory effects on contractile responses to clonidine (CL) and BHT than on responses to methoxamine (MO). In tissues treated with phenoxybenzamine, nicorandil (10(-5) M) inhibited residual responses to MO. The relationship between maximum contraction and percent-receptor occupancy was nonlinear for MO, but was near linear for CL and BHT. Prazosin had much greater inhibitory effect on responses to MO and CL than did yohimbine. Nicorandil only slightly inhibited the contractile response of both aorta and femoral arteries to K+ or excess Ca2+, while nifedipine (10(-6) and 10(-5) M) nearly abolished it. In a Ca2+-free medium containing EGTA, nicorandil (10(-7)-10(-5) M) inhibited residual responses of the aorta to BHT, CL, and MO in a concentration-dependent manner. The inhibitory effect of nicorandil was much greater on responses to BHT and CL than to MO. In addition, nicorandil (10(-7)-10(-5) M) inhibited the response of the aorta to Ca2+ (2 mM) added to a Ca2+-free medium containing EGTA, nifedipine (10(-6) M), and an agonist (BHT, CL, or MO). Furthermore, in aortae pretreated with phenoxybenzamine, nicorandil nearly abolished the residual response to MO in a Ca2+-free medium containing EGTA.(ABSTRACT TRUNCATED AT 250 WORDS)
D000316:Adrenergic alpha-Agonists / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil; D011817:Rabbits; D014665:Vasodilator Agents / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D014665:Vasodilator Agents; D009536:Niacinamide; D020108:Nicorandil; D002118:Calcium