On the histamine receptor of the canine myocardium and coronary vasculature.

To indentify the histamine-receptors in the canine myocardium, experiments were performed in the canine heart-lung preparation supported by a donor. Smaller doses of histamine produced only an increase in the coronary blood flow. Positive inotropic and chronotropic effects appeared with larger doses. The increase in the coronary blood flow was associated with only a minimal increase in the myocardial oxygen consumption. Pretreatment of the preparation with a prototype H1-receptor antagonist, mepyramine, resulted in an abolishment of the positive chronotropic effect and a partial inhibition of the coronary vasodilatatory effect, indicating that the histamine-receptors in the dog atrium subserving the chronotropic effect are to be classified as H1-type. After a representative H2-receptor antagonist, metiamide, the positive chronotropic effect remained unaffected, while there was a partial inhibition of the coronary vasodilatatory effect. A combined use of both the H1and H2-receptor antagonists brought about a complete suppression of the positive inotropic and the coronary vasodilatatory effects of histamine. These findings indicate that the hista mine-receptors in the coronary vasculature belong to the same type of receptors as those in the peripheral blood vessels, and that those in the canine ventricular myocardium cannot be classified either as H1 or H2. A preliminary report of this work was presented at the 50th Annual Meeting of the Japanese Pharmacological Society held in Tokyo on March 27-29, 1977. Gastric secretory and cardiac stimulatory effects of histamine which could not be blocked by classical antihystaminics have recently been reported to be blocked by a new type of compounds such as burimamide and metiamide and the receptor subserving these two effects of histamine have been classified as H,-type receptors (1-5), in contrast to the classical histamine receptor, which is now designated as ]-[,-type receptor. Although the later works performed with the atrial preparation of the guinea pig (6-7) suggested that the positive inotropic effect of histamine is mediated through H1-receptors, since the positive inotropic effects in the left atria are blocked by Hr-blocking agents, Reinhardt et al. (8) reached the conclusion that only H2-receptors exist in the ventricular myocardium, sub stantiating the initial findings of several investigators. Using the right ventricular strips of the guinea pig, Verma and McNeill (9) also suggested that the major histamine receptor in the ventricular myocardium of the guinea pig is of H2-type. H1-receptors are either few in number or do not have a high affinity for agonists. However, very recently, Chiba (10) reported that the positive inotropic and chronotropic effects of histamine in the isolated dog atrium perfused with arterial blood led from a carotid artery of the support dog were not blocked by selective H .,-receptor blocking agents, burimamide or metiamide, but significantly suppressed by an adequate dose of H,-receptor antagonist, tripelenamine or diphen