Antihypertensive activity of cadralazine in experimental hypertensive rats.

Antihypertensive and tachycardic activities of cadralazine were examined in experimental hypertensive rats (spontaneous, renal and deoxycorticosterone acetate-salt hypertension) after single or repeated oral administration, and compared with those of hydralazine. In single oral administration, cadralazine (0.3-5 mg/kg) produced a dose-related hypotensive effect and its maximum activity was equipotent to or more potent than that of hydralazine (1-5 mg/kg) in these hypertensive rats. The hypotensive effect of cadralazine appeared gradually and reached a maximum at 5-7 hr, while the maximum effect of hydralazine was observed at 1 hr after dosing. In SHR, the significant hypotensive effect of cadralazine persisted for 9-24 hr, but that of hydralazine lasted for only 1-12 hr. Therefore, there were marked differences in onset and duration of the hypotensive effect between cadralazine and hydralazine. Both drugs produced a dose-related tachycardic effect concomitant with the hypotensive effect. The separation ratios of cadralazine on these effects were equivalent to those of hydralazine. In repeated oral administration for 7 days, cadralazine (3 mg/kg/once a day) significantly reduced the daily starting blood pressure. The same response was obtained by 3 times daily repeated administration of hydralazine (3 mg/kg). Tolerance to the hypotensive and tachycardic effects was not observed during successive dosings of cadralazine or hydralazine. The potent and long lasting hypotensive effect of cadralazine might be useful for the treatment of arterial hypertension.