Duncker D J, Saxena P R, Verdouw P D
Department of Experimental Cardiology, Erasmus University Rotterdam, The Netherlands.
Eur J Pharmacol. 1988 Nov 8;156(3):401-9. doi: 10.1016/0014-2999(88)90286-5.
The systemic haemodynamic effects of a 10 min i.v. infusion of three dihydropyridine Ca2+ channel blockers, nifedipine (1, 2 and 4 micrograms.kg-1.min-1), nisoldipine (0.5, 1 and 2 micrograms.kg-1.min-1) and nimodipine (1, 2 and 4 micrograms.kg-1.min-1) were studied in instrumented conscious pigs with or without a propranolol-induced beta-adrenoceptor blockade (0.5 mg.kg-1 bolus followed by 0.5 mg.kg-1.h-1). Initial experiments showed that the solvent used for the Ca2+ channel blockers had no haemodynamic effects and that the effects of propranolol wer constant during a 30 min period. Nisoldipine, nimodipine and nifedipine elicited qualitatively similar effects, causing a dose-dependent decrease in blood pressure and systemic vascular resistance. These effects were accompanied by a reflex-mediated increase in heart rate, cardiac output and left ventricular rate of rise in pressure (LVdP/dtmax). Nisoldipine was about 2-3 times more potent than the other two drugs. Propranolol did not modify the vasodilation induced by the Ca2+ channel blockers but attenuated the increase in heart rate, cardiac output and LVdP/dtmax. In view of the reflex-tachycardia and the absence of negative inotropic actions, these Ca2+ channel blockers can be combined with beta-adrenoceptor antagonists without further compromising the left ventricular pump function.
在有或没有普萘洛尔诱导的β-肾上腺素能受体阻滞（0.5mg.kg-1静脉推注，随后0.5mg.kg-1.h-1）的仪器化清醒猪中，研究了静脉输注三种二氢吡啶类钙通道阻滞剂硝苯地平（1、2和4微克.kg-1.min-1）、尼索地平（0.5、1和2微克.kg-1.min-1）和尼莫地平（1、2和4微克.kg-1.min-1）10分钟的全身血流动力学效应。初始实验表明，用于钙通道阻滞剂的溶剂无血流动力学效应，且普萘洛尔的效应在30分钟内保持恒定。尼索地平、尼莫地平和硝苯地平产生了定性相似的效应，导致血压和全身血管阻力呈剂量依赖性降低。这些效应伴随着反射介导的心率、心输出量和左心室压力上升速率（LVdP/dtmax）增加。尼索地平的效力比其他两种药物强约2至3倍。普萘洛尔并未改变钙通道阻滞剂诱导的血管舒张，但减弱了心率、心输出量和LVdP/dtmax的增加。鉴于反射性心动过速以及缺乏负性肌力作用，这些钙通道阻滞剂可与β-肾上腺素能受体拮抗剂联合使用，而不会进一步损害左心室泵功能。
