ELECTROPHYSIOLOGICAL AND MECHANICAL STUDIES ON THE CARDIAC EFFECTS OF A HISTAMINE H2 RECEPTOR ANTAGONIST, CIMETIDINE, IN THE ISOLATED GUINEA PIG MYOCARDIUM

The effects of cimetidine, a new histamine H2 receptor antagonist, were studied electrophysiologically and mechanically in the isolated guinea pig myocardium. Cimetidine did not modify the electrical activity of the sinoatrial pacemaker cells at the concentrations up to 10-4 M, but depressed the pacemaker potential at the higher concentration, 3×10-4 M. Increase in the slope of the pacemaker potential produced by histamine was completely inhibited by cimetidine, indicating that the histamine receptor for the positive chronotropism is of H2-type. Cimetidine did not depress the maximum rate of rise of the atrial and ventricular action potentials ; thus, unlike most of the H1 receptor antagonists, cimetidine does not have quinidine like actions. The shape of the action potential was not modified significantly. Slow electrical and mechanical activities produced by histamine in the right ventricular myocardium whose fast Na+ channels were blocked by elevated external potassium were partially blocked by either cimetidine or diphenhydramine, supporting the view that both types of receptors are present in the right ventricle. Histamine-induced mechanical activity in the depolarized right atrium was inhibited by cimetidine, but that in the left atrium was not inhibited ; these results support the view that the histamine receptor in the left atrium is of H1-type and suggest that the histamine receptor for the positive inotropism in the right atrium is of H2-type. In addition, some results were shown suggesting the possibility that cimetidine might have some agonist-like action in the myocardium.