EFFECTS OF M-NIFEDIPINE ON CONTRACTILE RESPONSES IN THE ISOLATED ATRIA AND CORONARY VESSELS: A COMPARISON WITH NIFEDIPINE

For years calcium entry blockers have been of increasing importance in the therapy of cardiovascular diseases. In this paper, a potent dihydropyridine derivative M-nifedipine (M-Nif) had been studied. The purpose of this series of experiments was to compare the effect of M-Nif on the contractile response of isolated myocardium and coronary vessels with that of nifedipine (Nif). The left atria of guinea pigs were dissected out and suspended in an organ bath (20 ml) containing Krebs′ solution. Th resting tension was kept at 0.5 g. After an equilibration period of 1h, the bathing solution was switched to a high potassium (8.5 mM) and low calcium (0.6 mM) media. After a further equilibration period of 10min, cumulative concentration-response curves for calcium in atrial preparation were obtained. Then curves were determind in the presence of M-Nif 2.67×10^-7 and Nif 2.88×10^-7M. M-Nif and Nif reduced the maximum contractile response and shifted the concentration-response curves to the right in a non-parallel manner. The calcium antagonistic activity of Nif (PD₂′=7.19) was found to be stronger than that of M-Nif (PD′₂=7.05).M-Nif and Nif exhibited a concentration-dependent relaxant effect on the isolated atrial muscle preparations of the guinea pig. Nif (IC₅₀=2.9×10^-6M) was also 2.6 times more potent than M-Nif (IC₅₀=7.5×10^-6M).In contrast to the atrium, M-Nif and Nif showed nearly equipotent inhibitory effects on the isolated pig coronary vessel strips. However, M-Nif (PD′₂=7.06, IC₅₀=6.166×10^-7M) was slightly stronger (1.14 times) than Nif (PD′₂=6.88, IC₅₀=7.02×10^-7M). Therefore, it is concluded that M-Nif is a potent calcium antagonistic coronary vasodilator with less cardiodepresant effect as compared to Nif, which may be clinically useful as a vasodilator for treatment of congestive heart failure and possibly as a hypotensive agent.