Inhibitory Effects of Efonidipine Hydrochloride on Contraction Induced by Several Vasoconstrictors in Porcine Coronary Artery: Comparison with Effects of Nifedipine and Nisoldipine

We studied the effects of efonidipine hydrochloride (efonidipine), a 1,4-dihydropyridine derivative, on contractions induced by high-K+ solution (high K+), serotonin (5-HT), U46619, which is a stable analog of thromboxane A2, and endothelin-1 (ET-1) in comparison with those of nifedipine and nisoldipine in porcine coronary arteries. The effects of the drugs were compared after 1- and 3-h incubations. Efonidipine, nifedipine, and nisoldipine each inhibited the contractions induced by these vasoconstrictors. The inhibition of high-K(+)- and 5-HT-induced contractions by efonidipine, but not by nifedipine and nisoldipine, increased when the incubation time was prolonged, whereas the inhibition of U46619- and ET-1-induced contractions was not altered. The potency of efonidipine on U46619- and ET-1-induced contractions was greater than that of nifedipine and equivalent to that of nisoldipine. Thus the inhibitory effect of efonidipine on U46619- and ET-1-induced contractions seems to be stronger than its effects on high-K(+)- or 5-HT-induced contractions, in contrast to the effects of other dihydropyridines. In an additional series of experiments, efonidipine did not inhibit U46619-induced contractions in Ca2(+)-free solution or in the presence of nifedipine. Moreover, efonidipine did not inhibit the specific binding of [3H]SQ 29,548, a thromboxane A2 antagonist, to porcine coronary arterial membrane. Therefore we think that the inhibitory effect of efonidipine on contractions induced by vasoconstrictors was caused by blockade of Ca2+ influx through L-type Ca2+ channels. However, some unknown mechanism(s) in addition to this effect on Ca2+ channels may contribute to the effect of efonidipine on U46619- and ET-1-induced contractions.