Effect of Nicorandil, N-(2-Hydroxyethyl)nicotinamide Nitrate, a New Anti-Anginal Agent, on Contractile Responses to Alpha-1- and Alpha-2-Adrenoceptor Agonists in Isolated Rabbit Aorta

Abstract

Effects of nicorandil on contractile responses to α₁- and α₂adrenoceptor agonists were examined in isolated rabbit aorta. Nicorandil (10^–6 or 10^–5 M) inhibited contractile responses to clonidine (CL) and BHT-920 in a concentration-dependent manner, but had no effect on the response to methoxamine (MO). Nifedipine (10^–6 and 10^–5 M) had no significant effect on responses to CL and MO, but it had a noticeable inhibitory effect on the response to BHT-920. In tissues pretreated with phenoxybenzamine, nicorandil (10^–5 M) inhibited the residual response to MO, and nifedipine (10^–5 M) inhibited responses to MO and CL. The relationship between maximum contraction and percent receptor occupancy was found to be nonlinear for MO, but was near linear for CL and BHT-920. The inhibitory effect of prazosin (pA₂ of about 9) on MO and CL was much greater than that of yohimbine (pA₂ of about 6). Nicorandil had no apparent or slight inhibitory effect on responses to potassium and Ca²⁺, and this inhibitory effect was much less than that of nifedipine. These results indicate that the responses induced by MO, CL, and BHT-920 in the rabbit aorta are due to activation of α₁-adrenoceptors. It is also suggested that nicorandil minimally affects voltage-dependent Ca²⁺ influx and that differential effects of nicorandil on the responses to α₁ and α₂ agonists may be the result of differeneces in the amount of receptor reserve that exist for MO, CL, and BHT-920 in this blood vessel.