Acceleration of idioventricular rhythms by histamine in guinea pig heart: mediation by H2 receptors.
To evaluate the ability of histamine to induce ventricular arrhythmias, we studied the effects of histamine on ventricular rhythmicity in the isolated guinea pig heart with complete atrioventricular conduction block. As a function of dose (0.1-30 microgram), histamine enhanced the idioventricular rate by increasing the rate of firing of the original pacemaker and also by causing the sudden appearance of faster idioventricular rhythms that coincided with changes in pacemaker site. Anaphylaxis in the isolated guinea pig heart with complete atrioventricular conduction block caused histamine release and acceleration of idioventricular rate. The effects of histamine on idioventricular rhythmicity were not attenuated by the histamine H1 receptor antagonist chlorpheniramine, but were antagonized by the H2 receptor antagonist cimetidine. Moreover, the selective H2 agonist 4-methylhistamine (4MeH) accelerated the idioventricular rate, whereas 2-(2-thiazolyl) ethylamine (ThEA), at doses selective for H1 receptor activation, did not. The effects of histamine on idioventricular rhythmicity were not modified by the beta-adrenergic blocker pindolol. The mechanism by which histamine increases idioventricular rate probably involves two components: (1) an enhancement in automaticity of the original pacemaker, and (2) the induction of faster rhythms via reentry and/or afterdepolarizations. Whatever the mechanism, both components of the ventricular chronotropic action of histamine appear to involve exclusively histamine receptors of the H2 type. Thus, our results suggest that H2 receptor antagonists may have a role as specific antiarrhythmic agents in the treatment of cardiac dysfunctions caused by histamine release.
D000707:Anaphylaxis / Q000503:physiopathology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D002744:Chlorpheniramine / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006327:Heart Block / Q000503:physiopathology*; D006329:Heart Conduction System / Q000187:drug effects*; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology; D010869:Pindolol / Q000494:pharmacology; D011968:Receptors, Histamine / Q000502:physiology*; D011970:Receptors, Histamine H2 / Q000502:physiology*
D008761:Methylhistamines; D011968:Receptors, Histamine; D011970:Receptors, Histamine H2; D002744:Chlorpheniramine; D002927:Cimetidine; D006632:Histamine; D010869:Pindolol