Higashino R, Sato R, Jin H, Inoue N, Fukuta Y, Kurimoto T, Tamaki H
Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., Saitama, Japan.
J Cardiovasc Pharmacol. 1997 May;29(5):624-30. doi: 10.1097/00005344-199705000-00010.
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.
我们研究了1,4 - 二氢吡啶衍生物盐酸埃夫卡地平（埃夫卡地平）对猪冠状动脉中高钾溶液（高钾）、5 - 羟色胺（5 - HT）、血栓素A2的稳定类似物U46619以及内皮素 - 1（ET - 1）诱导的收缩作用，并与硝苯地平和尼索地平进行了比较。在孵育1小时和3小时后比较了这些药物的作用。埃夫卡地平、硝苯地平和尼索地平均抑制了这些血管收缩剂诱导的收缩。当孵育时间延长时，埃夫卡地平对高钾和5 - HT诱导收缩的抑制作用增强，而硝苯地平和尼索地平则无此现象，然而埃夫卡地平对U46619和ET - 1诱导收缩的抑制作用未改变。埃夫卡地平对U
46619和ET - 1诱导收缩的效力大于硝苯地平，与尼索地平相当。因此，与其他二氢吡啶类药物的作用相反，埃夫卡地平对U46619和ET - 1诱导收缩的抑制作用似乎强于其对高钾或5 - HT诱导收缩的作用。在另一系列实验中，埃夫卡地平在无钙溶液中或存在硝苯地平的情况下不抑制U46619诱导的收缩。此外，埃夫卡地平不抑制血栓素A2拮抗剂[3H]SQ 29,548与猪冠状动脉膜的特异性结合。因此我们认为，埃夫卡地平对血管收缩剂诱导收缩的抑制作用是由于通过L型钙通道阻断钙内流所致。然而，除了对钙通道的这种作用外，一些未知机制可能也参与了埃夫卡地平对U46619和ET - 1诱导收缩的作用。
