Separate receptors mediating the positive inotropic and chronotropic effect of histamine in guinea-pig atria

Abstract

The direct positive inotropic effect of histamine was studied on paced left atrial preparations from guinea pigs. Histamine (10 −8 to 10 −4 M) increased the maximum tension developed in left atria incubated at 35°C and driven at 2 Hz. The maximum increase in tension was 60% of that observed with norepinephrine. Metiamide (3 × 10 −5 M; a specific H 2-receptor antagonist) did not alter the inotropic response of left atria to histamine. However, tripelennamine (a typical H 1-receptor antagonist) competitively shifted the histamine inotropic dose—response curve to the right at concentrations from 10 −8 to 10 −7 M. Higher concentrations (3 × 10 −7 and 10 −6 M) caused little further additional shift to the right. The positive chronotropic effect of histamine on spontaneously beating atria was competitively antagonized by metiamide (10 −6 and 3 × 10 −6 M). These results demonstrate that in guinea-pig atria histamine increases myocardial contractility by an interaction with receptors closely related to classical H 1-receptors while its chronotropic effects is mediated by interaction with H 2-receptors.