Histamine - Induced Release of Endogenous Catecholamines in Rat Atria

Abstract

The chronotropic and inotropic actions of histamine were recorded from rat atria. Histamine (5 x 10^-4 to 10^-3 M) produced only the positive chronotropic action whereas at higher concentrations (>2.5 x l0^-3 M), a biphasic response characterized by a brief reduction in heart rate followed by a gradual increase in heart rate was observed in spontaneously beating right atria. Similar results were obtained when studying the inotropic actions of histamine on the paced left atria.

Propranolol (10^-6 M) and reserpine abolished the positive chronotropic and inotropic but not the negative chronotropic and inotropic actions of histamine. Diphenhydramine at a concentration of 5x10^-7 M, which failed to block the positive chronotropic action of norepinephrine, was effective in blocking the positive chronotropic action of histamine. Metiamide (5x10^-5 M) failed to alter the cardiac actions of histamine. We suggest that the cardiac stimulant actions of histamine in rat atria are the result of released-endogenous catecholamines.

Histamine alters the electrical and mechanical functions of isolated hearts of various species including, cat (1,2),  rabbit (1-3), guinea pig (2,4-6) and frog (7). Unlike the information available from other species, the observations of the cardiac actions of histamine in rat atria are very few and not consistent. For example, in Langendorff preparations, it has been reported that histamine produces negative inotropic and chronotropic actions (6), negative inotropic followed by marked positive inotropic action (8,9) and in isolated spontaneously beating right atria, a positive chronotropic action (10).

At present it is generally believed that the cardiac stimulant actions of histamine are mediated by its direct action on specific histamine receptors (2,5,11). However, in rats, it has been suggested that the effects of histamine were mainly a result of catecholamine release (8,9). Later it was reported that histamine released catecholamines in the dog heart-lung preparation, but only at high concentrations (12).

In the present work, we attempted to resolve these conflicting reports by using paced left atria to study the inotropic action of histamine and spontaneously beating right atria for studying the chronotropic action. Pharmacological intervention, including the use of reserpine, propranolol and antihistaminic agents were also employed in this study to elucidate whether the cardiac actions of histamine observed in rat atria were mediated by specific histamine receptors or by release of endogenous catecholamines.