In vitro effects of nifedipine, nisoldipine, and lacidipine on rat isolated coronary small arteries.

We investigated the effect of 1,4-dihydropyridine calcium antagonists (nifedipine, nisoldipine, and lacidipine) on serotonin (5-HT)- and KCl (120 mM)-induced contractions of rat isolated septal coronary artery. The preparations showed the well-known biphasic response to KCl depolarization. All three calcium antagonists were more potent in inhibiting the second, tonic phase compared to the first, transient phase, with pIC50 values of 7.17 +/- 0.12/8.27 +/- 0.07 (nifedipine), 7.93 +/- 0.21/8.96 +/- 0.06 (nisoldipine), and 8.28 +/- 0.07/9.79 +/- 0.04 (lacidipine) for suppressing the first and the second phase, respectively. Furthermore, the influence of the calcium antagonists on the 5-HT concentration-response curve was investigated. Nifedipine, nisoldipine, and lacidipine concentration dependently depressed the maximum effect of 5-HT on the coronary artery preparations without influencing the pEC50 of the 5-HT concentration-response curve. In conclusion, all three dihydropyridine calcium antagonists are potent and effective inhibitors of depolarization- or 5-HT-induced coronary artery contractions. Lacidipine, a new lipophilic compound, was the most potent one in inhibiting the depolarization-induced contraction, thereby showing a marked selectivity for the tonic phase compared to the initial phasic response.