Montastruc P, Valet P, Dang Tran L, Gaillard G, Montastruc J L
Laboratoire de Pharmacologie Médicale et Clinique (UA 644 du CNRS), Faculté de Médecine, Toulouse, France.
Fundam Clin Pharmacol. 1987;1(2):85-94. doi: 10.1111/j.1472-8206.1987.tb00548.x.
The hypotensive and negative chronotropic effects of 5 calcium entry blockers (verapamil 200 micrograms/kg IV; diltiazem 300 micrograms/kg IV; nifedipine 5 micrograms/kg IV; nicardipine 50 micrograms/kg IV; and bepridil 5 mg/kg IV) were compared in control normotensive and acute neurogenic hypertensive anaesthetized dogs. Acute neurogenic hypertension was induced by sino-aortic denervation (SAD). In control normotensive dogs, all drugs (except bepridil) induced a slight and transient decrease in blood pressure. Nifedipine and nicardipine increased heart rate whereas the three other drugs remained ineffective. SAD caused a 2-2.5-fold increase in the hypotensive properties of the 5 drugs in dogs. Moreover, the duration of this induced hypotension was longer than in control normotensive animals. In SAD dogs, all calcium entry blockers significantly decreased heart rate. This study indicates that the direct cardiac inhibitory action of calcium channel blockers is modulated by baroreceptor activity in intact animals. The mechanism of the selective action of calcium entry blockers in hypertensive SAD in contrast to normotensive dogs is discussed.
在对照正常血压和急性神经源性高血压麻醉犬中，比较了5种钙通道阻滞剂（维拉帕米200微克/千克静脉注射；地尔硫䓬300微克/千克静脉注射；硝苯地平5微克/千克静脉注射；尼卡地平50微克/千克静脉注射；苄普地尔5毫克/千克静脉注射）的降压和负性变时作用。急性神经源性高血压通过窦主动脉去神经支配（SAD）诱导产生。在对照正常血压犬中，所有药物（除苄普地尔外）均引起血压轻微且短暂下降。硝苯地平和尼卡地平使心率增加，而其他三种药物则无此作用。SAD使犬体内这5种药物的降压作用增强2至2.5倍。此外，这种诱导性低血压的持续时间比对照正常血压动物更长。在SAD犬中，所有钙通道阻滞剂均显著降低心率。本研究表明，在完整动物中，钙通道阻滞剂的直接心脏抑制作用受压力感受器活动调节。讨论了钙通道阻滞剂在高血压SAD犬与正常血压犬中选择性作用的机制。
