Pharmacological characterization of cardiac histamine receptors: sensitivity to H1-and H2-receptor agonists and antagonists.

In the isolated guinea pig heart, histamine H1-receptor antagonists inhibit the histamine-induced negative dromotropic effect, but not the positive inotropic and chronotropic effects (Levi and Kuye, 1974, European J. Pharmacol. 27, 330). Burimamide, the H2-receptor antagonist, inhibits the positive chronotropic effect of histamine (Black et al., 1972, Nature 236, 385). In this study, the hypothesis that H1- and H2-receptors selectively mediate the various cardiac effects of histamine was tested: (a) by investigating the inhibition of cardiac histamine effects by burimamide; (b) by studying the cardiac effects of 2-methylhistamine (an H1-agonist) and 4-methylhistamine (an H2-agonist). Burimamide, as a function of concentration, inhibited the positive inotropic and chronotropic effects of histamine, whereas it attenuated the negative dromotropic effect of histamine at the higher concentration only. 4-Methylhistamine caused dose-dependent positive inotropic and chronotropic but not negative dromotropic effects; conversely, with 2-methylhistamine the negative dromotropic effect prevailed. Sinus tachycardia and slowing of atrioventricular conduction were also obtained in the guinea pig in vivo by the i.v. administration of histamine. Burimamide selectively antagonized the positive chronotropic effect, whereas promethazine (an H1-antagonist) selectively inhibited the negative dromotropic effect. These results substantiate the hypothesis that H2-receptors mediate the histamine-induced increase in rate and contractility, whereas H1-receptors mediate the slowing of atrioventricular conduction.