Richer C, Lefevre-Borg F, Cadilhac M, Cavero I, Giudicelli J F
J Pharmacol. 1985 Jan-Mar;16(1):45-58.
The antihypertensive properties of nicardipine have been studied in various experimental models of hypertension. Furthermore, the possible contribution of the nicardipine-alpha-adrenergic system interaction to the drug's antihypertensive effect has been investigated. In the conscious normotensive rat, nicardipine (10 and 30 mg/kg, orally) reduces arterial blood pressure (by about 25%) and increases heart rate; these effects are maximal one hour after drug administration and disappear within 4 to 6 hours. In the renovascular hypertensive rat and in the Grollman hypertensive dog, nicardipine (3 mg/kg, orally) significantly decreases blood pressure. Simultaneously, heart rate is increased in the dog but is not significantly modified in the rat. In the conscious adult spontaneously hypertensive rat (SHR), nicardipine administered either as a bolus, or by intra arterial perfusion (1, 5, 12.5 micrograms/kg/min during 30 min), or orally (10, 30 mg/kg) dose-dependently decreases blood pressure and increases heart rate. In the pithed SHR, nicardipine decreases systemic pressor and regional (kidney, mesentery, hindlimb) vasopressor responses to M7, an alpha 2-adrenoceptor specific agonist, but does not affect those to cirazoline, an alpha 1-adrenoceptor specific agonist. However, there is no evidence for an involvement of this alpha 2-sympathoinhibitory effect in the blood pressure lowering action of nicardipine. In conclusion, in the different investigated experimental models of hypertension, nicardipine exerts a potent but short-lasting antihypertensive effect generally accompanied by a reflex tachycardia and a systemic and regional vascular alpha 2-sympathoinhibitory action.
已在多种高血压实验模型中研究了尼卡地平的降压特性。此外,还研究了尼卡地平与α-肾上腺素能系统相互作用对该药降压作用的可能贡献。在清醒的正常血压大鼠中,尼卡地平(口服10和30mg/kg)可降低动脉血压(约25%)并增加心率;这些作用在给药后1小时达到最大,并在4至6小时内消失。在肾血管性高血压大鼠和格罗曼高血压犬中,尼卡地平(口服3mg/kg)可显著降低血压。同时,犬的心率增加,但大鼠的心率无明显改变。在清醒的成年自发性高血压大鼠(SHR)中,尼卡地平以推注、动脉内灌注(30分钟内1、5、12.5μg/kg/min)或口服(10、30mg/kg)给药时,剂量依赖性地降低血压并增加心率。在脊髓横断的SHR中,尼卡地平可降低对α2-肾上腺素能受体特异性激动剂M7的全身升压和局部(肾脏、肠系膜、后肢)血管升压反应,但不影响对α1-肾上腺素能受体特异性激动剂可乐定的反应。然而,没有证据表明这种α2-交感神经抑制作用参与了尼卡地平的降压作用。总之,在不同的高血压实验模型中,尼卡地平发挥强效但作用短暂的降压作用,通常伴有反射性心动过速以及全身和局部血管的α2-交感神经抑制作用。