Differential Inhibitory Effects of Nicorandil, a New Antiangina Agent, on the Contractile Responses to Alpha-1- and Alpha-2-Adrenoceptor Agonists in Isolated Rabbit Renal and Femoral Arteries

Abstract

In the renal and femoral artery, nicorandil (10^–6–10^–4 mol/l) had a much greater inhibitory effect on the responses to clonidine (CL) and BHT-920 than on the response to methoxamine (MO) but the inhibitory action of nifedipine on the responses was not different. In the presence of nifedipine, nicorandil further inhibited the responses to all agonists. In the tissue pretreated with phenoxybenzamine, nicorandil inhibited the residual maximum response to MO in the femoral artery but not in the renal artery. Nicorandil had no effect on the residual response to high concentrations of MO in the renal artery pretreated with phenoxybenzamine and nifedipine. Relationship between maximum contraction and percent-receptor occupancy was found to be nonlinear for MO but was close to linear for CL. The inhibitory effect (PA2) of prazosin on MO and CL was much greater than that of yohimbine. In both preparations, nicorandil had only a slight inhibitory effect on the responses to potassium and Ca²⁺. It is concluded that the responses induced by MO, CL and BHT are due to activation of α₁-adrenoceptors and that the differential effect of nicorandil on the responses to α₁ and α₂-agonists may be the result of differences in the amount of receptor reserves and/or efficacy of receptor-contraction coupling that exists for MO, CL and BHT.