Inotropic effects of histamine in human myocardium: differentiation between positive and negative components.
Histamine is known to enhance the contractility of the human myocardium in vitro. We have observed that when the H2-receptor antagonist cimetidine (or ranitidine) blocks the positive inotropic effect of histamine in spontaneously beating pectinate muscles isolated from human right atrial appendage, a negative inotropic effect is unmasked. This decrease in contractility is independent of changes in rate, as it occurs in preparations paced at constant rate, is mimicked by the H1-receptor agonist 2-(2-thiazolyl)-ethylamine (ThEA) and is abolished by the H1-antagonist pyrilamine. Thus, the negative inotropic effect of histamine appears to be mediated by H1-receptors. Our data indicate that the inotropic response of the human myocardium to histamine consists of two opposing components: an increase in contraction, mediated by H2-receptors, and a decrease in contraction, mediated by H1-receptors. Given the widespread use of H2-blockers and the multitude of clinical conditions in which histamine is released, there may well be circumstances in which an H1-response predominates. This could result in a decrease in myocardial contractility.
D002927:Cimetidine / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D017446:Impromidine; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D011899:Ranitidine / Q000494:pharmacology; D011969:Receptors, Histamine H1 / Q000187:drug effects; D011970:Receptors, Histamine H2 / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors
D007093:Imidazoles; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D013844:Thiazoles; C029345:2-(2-aminoethyl)thiazole; D002927:Cimetidine; D006632:Histamine; D011899:Ranitidine; D017446:Impromidine; D011738:Pyrilamine; D009638:Norepinephrine