Davy M, Midol-Monnet M, Cohen Y, Wepierre J
Arch Int Pharmacodyn Ther. 1977 Dec;230(2):257-78.
The effects of intravenous dl-propranolol (5 mg/kg), 1- and d-alprenolol (5 mg/kg), on blood pressure, heart rate, cardiac output and total peripheral resistance were investigated in normotensive and spontaneously, renal or neurogenic hypertensive rats. The animals were either awake or anaesthetized with urethane, chloralose or pentobarbital. Anaesthesia may induce hemodynamic changes in hypertensive rats; thus urethane decreased peripheral vascular resistance in spontaneously hypertensive rats. In anaesthetized rats, dl-propranolol, 1- and d-alprenolol caused significant falls in blood pressure, heart rate and cardiac output. The hypotensive activity was related to the initial blood pressure. Peripheral vascular resistance remained unchanged except in spontaneously hypertensive, chloralose anaesthetized rats. 1-Alprenolol had less cardiac effects than dl-propranolol. The decrease of blood pressure was shorter and/or smaller after d-alprenolol than after 1-alprenolol. In normotensive and renal hypertensive awake rats, dl-propranolol induced a short fall of blood pressure, due to a decrease of heart rate and cardiac output. These effects, except bradycardia, were not observed in spontaneously hypertensive rats. These results suggest that differences in the initial vascular state, in the hypertensive models and in the anaesthetics used can explain the variability of the responses to beta-adrenergic blocking drugs. Moreover, beta-blocking as well as quinidine-like activities are involved in the cardiovascular responses to dl-propranolol, d-alprenolol and 1-alprenolol studied here.
研究了静脉注射dl-普萘洛尔（5毫克/千克）、左旋和右旋阿普洛尔（5毫克/千克）对正常血压以及自发性、肾性或神经源性高血压大鼠的血压、心率、心输出量和总外周阻力的影响。动物处于清醒状态或用乌拉坦、氯醛糖或戊巴比妥麻醉。麻醉可能会在高血压大鼠中引起血流动力学变化；因此，乌拉坦会降低自发性高血压大鼠的外周血管阻力。在麻醉大鼠中，dl-普萘洛尔、左旋和右旋阿普洛尔会导致血压、心率和心输出量显著下降。降压活性与初始血压有关。除了在自发性高血压、氯醛糖麻醉的大鼠中外，外周血管阻力保持不变。左旋阿普洛尔对心脏的影响小于dl-普萘洛尔。右旋阿普洛尔给药后血压下降的幅度比左旋阿普洛尔给药后更短和/或更小。在正常血压和肾性高血压清醒大鼠中，dl-普萘洛尔由于心率和心输出量的降低而导致血压短暂下降。在自发性高血压大鼠中未观察到这些作用，除了心动过缓。这些结果表明，高血压模型中初始血管状态以及所用麻醉剂的差异可以解释对β-肾上腺素能阻断药物反应的变异性。此外，β-阻断以及类似奎尼丁的活性参与了此处研究的dl-普萘洛尔、右旋阿普洛尔和左旋阿普洛尔的心血管反应。
