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[Antihypertensive effects of amlodipine, a new calcium antagonist].

The antihypertensive effects of oral administration of amlodipine (AML), a new calcium antagonist, were investigated in hypertensive animals. AML (1-10 mg/kg) produced a dose-dependent reduction of blood pressure (BP) in spontaneously hypertensive rats (SHR). The effect of AML reached a maximum at 4-6 hr and was sustained even at 10 hr post-dose, in contrast to the case of nifedipine that produced a maximum effect at 1 hr with a rapid recovery. Heart rate (HR) was increased slowly and slightly by AML (10mg/kg), but increased rapidly and markedly by nifedipine (3, 10 mg/kg). The dose (ED 30) of AML required to decrease BP by 30 mmHg was 2.3 mg/kg and similar to the case of nifedipine. AML also produced long-lasting reduction of BP in renal and DOCA hypertensive rats. The ED30 values were 2.4 and 2.2 mg/kg and similar to the respective values of nifedipine (ED 30:2.4,2.1 mg/kg). In renal hypertensive dogs (RHD), the effect of AML (0.1,0.3,1.0 mg/kg) was maximum at 4-6 hr and long-lasting, producing similar reductions of both systolic and diastolic BP (ED30: 0.3-0.4 mg/kg respectively). In SHR (1 or 3 mg/kg/day, for 15 days) and RHD (0.2 mg/kg/day for 20 days) chronically receiving AML, there was an enhancement of the antihypertensive effect of AML within a few days after starting chronic dosing, and thereafter a significant reduction of BP at 24 hr after dosing and constant effects of AML during subsequent treatment. BP after cessation of the chronic dosing gradually recovered to the level before the start of the experiments. No significant changes in HR were observed throughout the experiments. These results indicate that AML produces the antihypertensive effect with a similar potency to nifedipine but with a profile of slow onset and long duration, and there was no development of tolerance to the antihypertensive effects and changes of HR during long-term treatment.