【摘要】 M-Nif对离体豚鼠左心房的钙拮抗作用PD₂^′=7.05较Nif PD₂^′=7.19弱,抑制心肌的IC₅₀=7.5×10^-8M亦较Nif IC₅₀=2.9×10^-6M弱2.6倍。在离体猪冠脉条实验中M-Nif PD₂^′=7.06,Nif PD₂^′=6.88,前者稍强,前者抑制血管的作用IC₅₀=6.166×10^-7M亦强于后者IC₅₀=7.02×10^-7M 114倍,Nif扩张血管作用较抑制心肌作用强10倍,提示M-Nif扩张血管与抑制心肌的宽度更大,对治疗心力衰竭、降压将更有利。更多还原

【Abstract】 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.更多还原