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

The H2-receptor antagonist cimetidine (250 micrograms) administered intracerebroventricularly (i.c.v.) 15 and 30 min before clonidine (25 micrograms 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 micrograms i.c.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.