Bkaily G, Molyvdas P A, Ousterhout J, Sperelakis N
Eur J Pharmacol. 1986 May 13;124(1-2):59-65. doi: 10.1016/0014-2999(86)90124-x.
The effects of the dihydropyridine analogs, nilvadipine (FR-34235) and mesudipine, on the electrical activity of rat aortic smooth muscle cells in culture (reaggregates) were compared with the calcium antagonist verapamil. Nilvadipine blocked the tetraethylammonium-induced action potentials (APs), whose inward current is carried almost exclusively by Ca2+ through voltage-dependent slow channels. The effects of nilvadipine were dose dependent, and nilvadipine had a more potent inhibitory effect on the K+-induced contraction than on the norepinephrine-induced contraction of rabbit aorta. The ED50 value for blockade of the K+-induced contracture by nilvadipine was 6.4 X 10(-8) M, and complete blockade of the Ca2+ slow channels occurred at 10(-8) M. Mesudipine also inhibited the Ca2+ slow channels in cultured vascular smooth muscle cells in a dose-dependent manner; elevation of the [Ca]O from 1.8 to 5.4 mM partially restored the slow APs. The order of the inhibitory action on the Ca2+-dependent slow APs was: nilvadipine greater than mesudipine greater than verapamil. The inhibition of Ca2+ influx during excitation by the drugs can account for their vasodilatory properties.
将二氢吡啶类似物尼伐地平（FR - 34235）和美舒地尔平对培养的大鼠主动脉平滑肌细胞（重聚体）电活动的影响与钙拮抗剂维拉帕米进行了比较。尼伐地平阻断了四乙铵诱导的动作电位（APs），其内向电流几乎完全由Ca2+通过电压依赖性慢通道携带。尼伐地平的作用具有剂量依赖性，并且尼伐地平对兔主动脉K+诱导的收缩的抑制作用比对去甲肾上腺素诱导的收缩更强。尼伐地平阻断K+诱导挛缩的ED50值为6.4×10（-8）M，在10（-8）M时Ca2+慢通道完全被阻断。美舒地尔平也以剂量依赖性方式抑制培养的血管平滑肌细胞中的Ca2+慢通道；将[Ca]O从1.8 mM升高到5.4 mM可部分恢复慢动作电位。对Ca2+依赖性慢动作电位的抑制作用顺序为：尼伐地平＞美舒地尔平＞维拉帕米。药物在兴奋过程中对Ca2+内流的抑制作用可解释它们的血管舒张特性。
