Histamine-induced negative inotropism: mediation by H1-receptors.
Histamine is known to enhance left ventricular contractility in the guinea-pig heart by interacting with H2-receptors. We have observed that when the H2-receptor antagonists metiamide and cimetidine (3 X 10(-6) and 10(-5) M) block the positive inotropic effect of histamine, a negative inotropic effect is unmasked. This negative inotropic effect is independent of changes in rate or coronary flow, is mimicked by the selective histamine H1-receptor agonists, pyridylethylamine and thiazolylethylamine (0.3--30 microgram) and is abolished by the H1-receptor antagonist chlorpheniramine (10(-7) and 10(-6) M). Thus, the negative inotropic effect of histamine appears to be mediated by H1-receptors. Our results demonstrate that the inotropic response to histamine consists of two opposing components: an increase in contraction, mediated by H2-receptors, and a decrease in contraction, mediated by H1-receptors.
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003864:Depression, Chemical; D004347:Drug Interactions; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D011968:Receptors, Histamine / Q000187:drug effects*; D011969:Receptors, Histamine H1 / Q000187:drug effects*
D011968:Receptors, Histamine; D011969:Receptors, Histamine H1; D006632:Histamine