Warltier D C, Zyvoloski M G, Gross G J, Brooks H L
J Pharmacol Exp Ther. 1984 Aug;230(2):367-75.
The cardiovascular effects of the dihydropyridine slow channel calcium blocking agents, nifedipine, nitrendipine, FR 34235, niludipine and nisoldipine were compared to the vasodilator, hydralazine, in conscious, instrumented dogs before and after propranolol (2 mg/kg i.v.). The calcium-blocking agents (1.0, 2.5, 5.0, 10.0 and 25.0 micrograms/kg/min i.v.) and hydralazine (0.01, 0.025, 0.05, 0.10 and 0.25 mg/kg/min i.v.) produced dose-related decreases in blood pressure and reflex increases in heart rate and heart rate-systolic pressure product, an index of myocardial oxygen consumption. Hydralazine also produced a reflex increase in myocardial contractility (+dP/dt); however, minimal changes in contractility were observed with the dihydropyridines. Nisoldipine, nitrendipine and FR 34235 were relatively more effective in reducing arterial pressure than niludipine, nifedipine and hydralazine. For any given reduction in pressure, hydralazine produced the greatest reflex tachycardia at low doses. Of the calcium channel blockers, nifedipine produced the greatest and niludipine the least reflex tachycardia. Propranolol attenuated the reflex increase in heart rate and rate-pressure product produced by all vasodilators studied. Only slight changes in global contractility were observed after combined use of the dihydropyridines and propranolol. Nisoldipine, FR 34235 and nifedipine produced the greatest coronary vasodilation whereas niludipine, nitrendipine and hydralazine were less effective. In addition, the dihydropyridines produced a greater increase in systolic than diastolic flow. The present results demonstrate that while all dihydropyridine calcium channel blocking agents exhibit many similarities, certain differences exist. Furthermore, the "reflex" tachycardia observed with these drugs was not solely related to the degree of reduction in arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
在给予普萘洛尔（2毫克/千克静脉注射）前后，将二氢吡啶类慢通道钙阻滞剂硝苯地平、尼群地平、FR 34235、尼鲁地平与尼索地平的心血管效应，与血管扩张剂肼屈嗪在清醒、装有仪器的犬体内进行比较。钙阻滞剂（1.0、2.5、5.0、10.0和25.0微克/千克/分钟静脉注射）和肼屈嗪（0.01、0.025、0.05、0.10和0.25毫克/千克/分钟静脉注射）可使血压呈剂量依赖性下降，并使心率和心率-收缩压乘积反射性升高，心率-收缩压乘积是心肌耗氧量的一个指标。肼屈嗪还可使心肌收缩力反射性增强（+dP/dt）；然而，二氢吡啶类药物对收缩力的影响极小。与尼鲁地平、硝苯地平和肼屈嗪相比，尼索地平、尼群地平和FR 34235在降低动脉压方面相对更有效。对于任何给定的血压降低幅度，肼屈嗪在低剂量时产生的反射性心动过速最大。在钙通道阻滞剂中，硝苯地平产生的反射性心动过速最大，而尼鲁地平产生的最小。普萘洛尔减弱了所有研究的血管扩张剂所产生的心率和心率-压力乘积的反射性升高。联合使用二氢吡啶类药物和普萘洛尔后，整体收缩力仅有轻微变化。尼索地平、FR 34235和硝苯地平产生的冠状动脉扩张最大，而尼鲁地平、尼群地平和肼屈嗪的效果较差。此外，二氢吡啶类药物使收缩期血流增加的幅度大于舒张期血流。目前的结果表明，虽然所有二氢吡啶类钙通道阻滞剂表现出许多相似之处，但也存在某些差异。此外，这些药物所观察到的“反射性”心动过速并非仅与动脉压降低的程度有关。（摘要截短于250字）
