Role of histamine H1-and H2-receptors in the cardiovascular system of the rabbit.

The effects of histamine were examined on the circulation of the blood-perfused heart, kidney, intestine, and hindlimb of rabbits. Single intrarterial injections of drugs were made into the perfusion system of the coronary, renal, mesenteric, or femoral vascular bed. In the hearts, histamine caused dose-dependent positive inotropic and chronotropic responses and vaso-constriction. 2-Methylhistamine, a relatively selective histamine H1-receptor agonist, produced vascular effects very similar to those of histamine, but had no cardiac actions at low and negative inotropic responses at high doses. 4-Methylhistamine, a relatively selective histamine H2-receptor agonist, induced slight vasodilatation and positive inotropic and chronotropic responses. In the renal, mesenteric, and femoral vascular beds, histamine and 2-methylhistamine caused vasoconstriction, while 4-methylhistamine induced slight vasodilatation. Mepyramine, a selective H1-receptor antagonist, blocked the vasoconstriction in response to histamine and 2-methylhistamine, but not the positive inotropic and chronotropic responses to histamine. The combined action of mepyramine and cimetidine (a selective H2-receptor antagonist) eliminated all cardiac and vascular effects of histamine. These results strongly support the view that in the cardiovascular system of the rabbit, H1-receptors mediate negative inotropic effects and vasoconstriction, whereas H2-receptors are responsible for positive inotropic and chronotropic effects and vasodilatation.