Kubo T, Fujie K, Yamashita M, Misu Y
J Pharmacobiodyn. 1981 Apr;4(4):294-300. doi: 10.1248/bpb1978.4.294.
Hypotensive actions of single and repeated administrations of nifedipine were evaluated in comparison with hydralazine in normotensive, spontaneously hypertensive and renal hypertensive rats. Substantial and prolonged falls in blood pressure were observed following oral dosing with 3 mg/kg of nifedipine in renal hypertensive rats, with 10 mg/kg of nifedipine in normotensive and spontaneously hypertensive rats and with 10 mg/dg of hydralazine in all three groups of animals. The hypotensive effect of nifedipine was greater in both forms of hypertensive rats than the normotensive rats, while there was no difference in the hypotensive effect of hydralazine in normotensive and hypertensive animals. In spontaneously hypertensive rats tolerance to nifedipine and hydralazine was not observed with oral administrations for 4 weeks at a daily dose of 10 mg/kg. An increase in heart rate always accompanied the hypotension induced by both drugs, but this tachycardia was seen to a lesser extent with nifedipine than with hydralazine. The mechanism of the selective action of nifedipine in hypertensive rats in contrast to normotensive rats is discussed.
将硝苯地平单次及重复给药的降压作用与肼屈嗪进行比较，评估其在正常血压大鼠、自发性高血压大鼠和肾性高血压大鼠中的作用。在肾性高血压大鼠中，口服3mg/kg硝苯地平后观察到血压显著且持续下降；在正常血压大鼠和自发性高血压大鼠中，口服10mg/kg硝苯地平后血压下降；在所有三组动物中，口服10mg/dg肼屈嗪后血压下降。硝苯地平对两种高血压大鼠的降压作用均强于正常血压大鼠，而肼屈嗪在正常血压和高血压动物中的降压作用无差异。在自发性高血压大鼠中，每日口服10mg/kg，连续给药4周，未观察到对硝苯地平和肼屈嗪的耐受性。两种药物引起的低血压均伴有心率增加，但硝苯地平引起的心动过速程度低于肼屈嗪。讨论了硝苯地平在高血压大鼠与正常血压大鼠中选择性作用的机制。
