A positive inotropic response of guinea pig isolated atria to histamine not mediated via H1 or H2 receptors

Abstract

The positive chronotropic responses of guinea pig isolated right atria to histamine were antagonized by metiamide (pA2 [effective concentration of agonist to antagonist], 5.95), confirming their H2 receptor classification. The positive inotropic responses of paced left atria were antagonized to some extent by mepyramine to give a pA2 value of 7.87, indicating the involvement of H1 receptors. A limit to the shift of cumulative dose-response curves for the inotropic response suggested an H1 receptor resistant component. The inotropic response to sequentially administered histamine was biphasic. On lowering the temperature to 25.degree. C, the 2 components became more demarcated and separated by a negative phase. Only the primary positive component and the negative component were antagonized by mepyramine. At 38.degree. C, the response was similarly converted to a monophasic one. The residual responses were resistant to metiamide and propranolol antagonism and therefore not mediated via H1, H2 or .beta.-adrenergic receptors.