DELETERIOUS EFFECTS OF CIMETIDINE IN THE PRESENCE OF HISTAMINE ON CORONARY CIRCULATION - POSSIBLE CLINICAL IMPLICATIONS IN ANAPHYLACTIC STATES IN INDIVIDUALS WITH CORONARY HEART-DISEASE

Effects of histamine in the presence of the H2-antagonist cimetidine on the coronary circulation of the isolated perfused spontaneously beating guinea pig heart were studied. Infusion of histamine (2 .times. 10-8 mol/l-5 .times. 10-6 mol/l) induced a dose-dependent coronary dilation, comparable to the effect of isoproterenol and 2 highly selective H2-agonistic compounds, impromidine and dimaprit. In the presence of cimetidine (5 .times. 10-6 mol/l), 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 .times. 10-7 mol/l, whereas the dilatory effect of impromidine and dimaprit was completely antagonized. The histamine-induced constriction in the presence of cimetidine could be nearly abolished by additional infusion of the H1-antagonistic compound mepyramine (5 .times. 10-5 mol/l). H1- and H2-receptors are apparently present in the coronary smooth muscle, H1-receptors mediating constriction and H2-receptors mediating coronary dilation. Histamine may have hazardous effects in anaphylactic states in humans if cimetidine is administered simultaneously, e.g., to prevent or cure peptic ulcer. Other possible clinical implications are discussed.