Peripheral hypotensive and central hypertensive effects of cimetidine

Rapid intravenous (i.v.) injections of high doses (16-128 mumol/kg) of cimetidine induced a short-lasting (5-15 min) hypotension in anaesthetized rats. Diastolic pressure was reduced more than systolic pressure, suggesting vasodilatation. Heart rate was not affected. Diphenhydramine pretreatment (100 mumol/kg i.v.) did not antagonize the hypotensive effect of cimetidine. However, in the presence of diphenhydramine, cimetidine induced bradycardia. Intracerebroventricular administration of cimetidine or metiamide (2 mumol/rat) increased the blood pressure and heart rate. It is concluded that the hypotension after i.v. cimetidine is mediated by peripheral mechanisms. Since diphenhydramine pretreatment had no antagonistic effect cimetidine-induced hypotension could not be due to indirect H1-receptor stimulation caused by histamine liberation.