Mechanism of direct cardiostimulating actions of hydralazine.
Mechanism of direct cardiostimulating actions of hydralazine.
复制标题
肼屈嗪的直接心脏刺激作用机制。
DOI：
10.1016/0014-2999(87)90605-4
复制
发表时间：
1987
影响因子：
5
通讯作者：
Sperelakis,N
中科院分区：
文献类型：
--
作者：
Azuma,J;Sawamura,A;Harada,H;Awata,N;Kishimoto,S;Sperelakis,N
据报告，血管扩张剂肼苯哒嗪在高浓度下也对心肌产生直接正性肌力作用。在本研究中，我们通过使用离体灌流鸡心脏的心室肌来研究这种正性变力作用的机制。肼苯哒嗪（10− 3 M）增强了收缩力和心率，并提高了心肌环磷酸腺苷水平。为了研究Ca 2+依赖性慢动作电位，用升高的K+（25 mM）对快N+通道进行电压失活，导致电兴奋性丧失。肼屈嗪（10− 4 M）快速（< 3分钟）允许通过电刺激产生慢动作电位和伴随的收缩。肼苯哒嗪的这些作用仅部分被普萘洛尔阻止。结果表明，肼苯哒嗪引起的心肌收缩力增加至少部分是对心肌的直接作用增加Ca 2+流入的结果。Ca ~（2+）内流和内向慢电流的增加部分是由于β-肾上腺素能受体的激活，导致cAMP的升高，部分是由于另一种机制。
The vasodilator, hydralazine, was reported to also exert a direct positive inotropic effect on the myocardium at high concentrations. In the present study we investigated the mechanism of this positive inotropic action by using the ventricular myocardium of isolated perfused chick hearts. Hydralazine (10−3M) enhanced contractile force and heart rate, and elevated the myocardial cyclic AMP level. To study the Ca2+-dependent slow action potentials, the fast N+channels were voltage-inactivated with elevated K+(25 mM), resulting in a loss of electrical excitability. Hydralazine (10−4M) rapidly (< 3 min) allowed the generation of slow action potentials and accompanying contractions by electrical stimulation. These effects of hydralazine were only partially prevented by propranolol. The results suggest that the increase of myocardial contractility produced by hydralazine is the result, at least in part, of a direct effect on the myocardium to increase Ca2+inflow. The increased Ca2+influx and inward slow current is due partly to activation of β-adrenoceptors, with resultant elevation of cyclic AMP, and partly to another mechanism.