The interaction of Cimetidine with various antihypertensive agents in the spontaneously hypertensive rat

Abstract

Abstract The H2-receptor antagonist Cimetidine (250 μg) administered intracerebroventricularly (i.e.v.) 15 and 30 min before Clonidine (25 μg kg−1 i.v.), significantly antagonized clonidine-induced hypotension in anaesthetized spontaneously hypertensive rats. The hypertensive response of Cimetidine was correlated with the inhibition of clonidine-induced hypotension. In addition, Cimetidine (250 μg i.e.v.) counteracted the hypotensive effects of pentolinium (5.0 mg kg−1 i.v.), guanethidine (5.0 mg kg−1 i.v.) and minoxidil (1.0 mg kg−1 i.v.) These data do not support previous suggestions that the hypotensive action of Clonidine is caused by stimulation of the H2-receptor, but suggest that central administration of Cimetidine causes peripheral vasoconstriction and this may offer resistance to the hypotensive action of different antihypertensive agents.