Deleterious effects of cimetidine in the presence of histamine on coronary circulation

Abstract

The present study characterizes effects of histamine in the presence of the H₂-antagonist cimetidine on the coronary circulation of the isolated perfused spontaneously beating guinea pig heart. Infusion of histamine (2 ⋅ 10⁻⁸ mol/1–5 ⋅ 10⁻⁶ mol/l) induced a dose-dependent coronary dilation, comparable to the effect of isoproterenol and two highly selective H₂-agonistic compounds, impromidine and dimaprit. In the presence of cimetidine (5 ⋅ 10⁻⁶ mol/l), however, coronary response to histamine was reversed in a manner that a dose-dependent coronary constriction occurred with coronary spasm and a flow rate approaching zero at histamine concentrations above 8 ⋅ 10⁻⁷ mol/l, whereas the dilatory effect of impromidine and dimaprit was completely antagonized. In contrast, the histamine-induced constriction in the presence of cimetidine could be nearly abolished by additional infusion of the H₁-antagonistic compound mepyramine (5 ⋅ 10⁻⁵ mol/l). Is is concluded that H₁- and H₂-receptors are present in the coronary smooth muscle, H₁-receptors mediating constriction and H₂-receptors mediating coronary dilation. Speculation is provided that histamine may have hazardous effects in anaphylactic states if cimetidine is administered simultaneously, e.g., to prevent or cure peptic ulcer. Other possible clinical implications will be discussed.