Chlorpromazine interactions with guanethidine and alpha-methyldopa: effects on arterial pressure control and heart rate in renovascular hypertensive rats.

The ability of chlorpromazine to impair the anti-hypertensive effectiveness of guanethidine or alpha-methyldopa was evaluated in one-kidney, one clip and two-kidney, one clip renovascular hypertensive rat models. Subacute blood pressure studies were conducted using chronically hypertensive rats receiving guanethidine (50 mg/kg/day) or alpha-methyldopa (100 mg/kg/day). Incremental doses of chlorpromazine (1, 3 and 10 mg/kg/day) for five consecutive days per dose were added to the antihypertensive regimen. Chlorpromazine (10 mg/kg/day) reversed the antihypertensive effect of guanethidine equally in both hypertensive models but did not alter guanethidine-induced bradycardia. Chlorpromazine did not impair the hypertensive effectiveness of alpha-methyldopa in either hypertensive rat model. These findings demonstrate the utility of the renovascular hypertensive rat models studied for investigating cardiovascular drug interactions with guanethidine and document the interactive potential of chlorpromazine with guanethidine or alpha-methyldopa in these hypertensive models.