Effects of the H1-antagonist promethazine and the H2-antagonist burimamide on chronotropic, inotropic and coronary vascular responses to histamine in isolated perfused guinea-pig hearts

Abstract

On guinea-pig atria part of the inotropic response to histamine is attributable to a concomitant increase of the frequency [7]. Since the chronotropic effect of histamine is mediated by a stimulation of H2-receptors a direct interaction of histamine with H1-receptors a direct interaction of histamine with H1-receptors mediating the inotropic response on heart may be overlooked. For this reason the ability of the H1-antagonist promethazine and the H2-antagonist burimamide to inhibit the positive chronotropic, inotropic and coronary vascular responses to histamine was determined in spontaneously beating and electrically driven perfused guinea-pig hearts. (1) Burimamide produced a competitive blockade of the positive chrono- and inotropic responses to histamine. (2) On the other hand, promethazine in concentrations that had no effect on cardiac function by itself, proved to be ineffective against the positive chrono- and inotropic responses produced by histamine on spontaneously beating and electrically driven heart preparations. (3) The predominant coronary vasodilation observed after infusion with histamine was competitively antagonized by promethazine and burimamide. This blockade was not attributable to an interaction with myocardial H2-receptors mediating increases in heart rate and contractility and was, therefore, direct in nature. (4) Based upon the present study and former investigations [7] the following distribution of different histamine receptors in the guinea-pig heart does exist: H1-receptors are present in the atrial muscle and the coronary vascular bed. H2-receptors are located in the sinus node, the ventricular myocardium and the coronary vessels.