CHRONOTROPIC AND INOTROPIC EFFECTS OF HISTAMINE IN DEVELOPING CHICK HEART - DIFFERENTIAL MECHANISMS BEFORE AND AFTER HATCHING

Chronotropic and inotropic effects of histamine were examined in isola ted atrial and ventricular preparations from embryonic and hatched chi cken hearts. Histamine produced positive chronotropic and inotropic re sponses both in embryonic and hatched hearts. The responses to histami ne in middle embryonic myocardia, which were observed in the micromola r range, were antagonized by H-2 antagonists but not by H-1, H-3 antag onists and propranolol. Isobutyl-methylxantine, an inhibitor of phosph odiesterase, produced a leftward shift of the concentration-response c urve for the chronotropic effect of histamine in the embryo. The respo nses to histamine in myocardia from hatched chicks, which were observe d in the milimolar range, appeared concurrently with the responses to tyramine during development and were antagonized by beta adrenoceptor antagonists but not by any of the histamine antagonists. The positive inotropic response to histamine in hatched ventricular preparations we re greatly attenuated by reserpine pretreatment or in the presence of desipramine. Thus, we demonstrated that exogenously applied histamine produces positive chronotropic and inotropic responses in developing c hicken hearts and that the mechanisms are different between embryonic and hatched chicks: direct action on H-2 receptors in the embryonic he art and release of norepinephrine from sympathetic nerve terminals in hatched hearts.