DIFFERENTIATION OF THE ROLES OF HISTAMINE Hr AND H2‐RECEPTORS IN THE MEDIATION OF THE EFFECTS OF HISTAMINE IN THE ISOLATED WORKING HEART OF THE GUINEA‐PIG

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Abstract
Differentiation of the rôles of histamine Hr and H2‐receptors in the mediation of the effects of histamine on the isolated working heart of the guinea‐pig was achieved through the use of histamine and selective histamine receptor agonists and antagonists. Histamine over the dose range 10−9mol to 10−6mol produced dose‐related increases in sinus rate, left intraventricular pressure (LVP)max, LVdP/dtmax, coronary flow, aortic flow, total cardiac output and external pressure‐volume work. Dimaprit, a selective histamine H2‐receptor agonist, produced very similar responses to histamine. 2‐Pyridylethylamine, a selective histamine Hj‐receptor agonist, had little effect on cardiac function unless large doses were administered. Such doses produced increases in all measured parameters. Cimetidine, a selective histamine H2‐receptor antagonist, antagonized the effects of histamine and dimaprit and some but not all effects of 2‐pyridylethylamine. In the presence of cimetidine a decrease in all parameters with the exception of sinus rate was observed with both histamine and 2‐pyridylethylamine. The selective histamine Hi‐receptor antagonist, mepyramine, had little effect on responses to all three agonists. However, the depressant effects observed with histamine and 2‐pyridylethylamine in the presence of cimetidine were antagonized by mepyramine. The results indicate the important rôle of the histamine H2‐receptor in the mediation of the gross cardiac effects of histamine and also indicate that histamine Hx‐receptors can mediate cardiac depression.