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.
Pfaffendorf
M
M
Department of Pharmacotherapy, University of Amsterdam, The Netherlands.
Mathy
M J
MJ
van Zwieten
P A
PA
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects*; D004095:Dihydropyridines / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D015737:Nisoldipine / Q000494:pharmacology; D011189:Potassium Chloride / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D012702:Serotonin Antagonists / Q000494:pharmacology; D012984:Software; D014661:Vasoconstriction / Q000187:drug effects
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D012702:Serotonin Antagonists; C060285:lacidipine; D015737:Nisoldipine; D011189:Potassium Chloride; D009543:Nifedipine