Characterization of the Coronary Vascular Response to Histamine in Rabbit Hearts Using Cimetidine

Abstract

Successive applications of histamine in the isolated, perfused rabbit heart revealed a transient constriction of coronary vasculature. The mechanism of this vasoconstriction, in particular its tachyphylactic nature, was the subject of this study. Diphenhydramine, perfused during one of the applications of histamine, blocked the vasoconstriction, indicating an H2-receptor-mediated response. Cimetidine, perfused during one of the applications of histamine, enhanced the vasoconstriction, indicating that H2-receptors mediate an inhibition of vasoconstriction. Cimetidine perfused during all applications of histamine reduced, and in some cases eliminated, the apparent tachyphylaxis, implying that the waning vasoconstrictor response normally seen with histamine was due to a gradually increasing H2-receptor-mediated inhibition.