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.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D002927:Cimetidine / Q000008:administration & dosage / Q000494:pharmacology*; D004155:Diphenhydramine / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014665:Vasodilator Agents
D006146:Guanidines; D014665:Vasodilator Agents; D002927:Cimetidine; D004155:Diphenhydramine