Effects of ranitidine and cimetidine on automaticity in isolated myocardium of guinea pig

At 0.1-30 mumols/L, neither ranitidine (Ran) nor cimetidine (Cim) inhibited the rate of spontaneous contraction in isolated right atria of guinea pig. When the concentration was higher than 100 mumols/L, both Ran and Cim exhibited weak negative chronotropic effects with IC50 of 109 +/- 3 and 436.5 +/- 1.9 mumols/L, respectively. However, the positive chronotropic effects of histamine (H) were markedly antagonized by Ran and Cim with IC50 of 0.40 +/- 0.29 and 1.8 +/- 0.6 mumols/L respectively. Ran (0.1 mumols/L) and Cim (1 mumols/L) competitively antagonized the concentration-dependent response of positive chronotropic effect mediated by H and had no influence on that induced by isoproterenol in right atria of guinea pig. Ran (10 mumols/L) and Cim (50 mumols/L) prevented the abnormal automaticity elicited by H and H (0.12 +/- 0.09 mumols/L) + Oua (0.04 +/- 0.02 mumols/L) which acted synergically. The abnormal automaticity induced by Oua (1.5 +/- 2.3 mumols/L) was antagonized by Ran (10 mumols/L) and not by Cim (50 mumols/L). Our results suggest that these effects of Ran and Cim are mainly attributed to cardiac H2 receptor blockade.