Sawamura A, Sperelakis N, Azuma J, Harada H, Fukuda K
J Pharmacol Exp Ther. 1986 Jan;236(1):192-6.
Electrophysiological studies on the cardiac effects of a H2-antagonist, cimetidine, were examined in three kinds of preparations: guinea-pig papillary muscles, rat left atria and perfused chick hearts. Cimetidine (10(-5) to 10(-4) M) depressed or abolished the slow action potentials (APs) induced by histamine (10(-5) to 10(-4) M) in hearts whose fast Na+ channels had been inactivated by 25 mM K+. Higher concentrations of cimetidine (10(-3) to 5 X 10(-3) M) increased myocardial cyclic AMP level and allowed the generation of slow APs in such inexcitable tissues. These cimetidine-induced slow APs were not prevented by propranolol (10(-6) to 10(-5) M) or pretreatment with 6-hydroxydopamine (50 mg/kg). These results suggest that cimetidine, in doses higher than that required to block cardiac H2-receptors, may have a cardio-stimulating action mediated through increase of inward Ca++ current.
在三种实验制剂中研究了H2拮抗剂西咪替丁对心脏的电生理作用：豚鼠乳头肌、大鼠左心房和灌注鸡心。在快速Na+通道已被25 mM K+灭活的心脏中，西咪替丁（10^(-5)至10^(-4) M）抑制或消除了组胺（10^(-5)至10^(-4) M）诱导的慢动作电位（AP）。更高浓度的西咪替丁（10^(-3)至5×10^(-3) M）可提高心肌环磷酸腺苷水平，并使此类不应激组织中产生慢动作电位。普萘洛尔（10^(-6)至10^(-5) M）或用6-羟基多巴胺（50 mg/kg）预处理并不能阻止这些西咪替丁诱导的慢动作电位。这些结果表明，高于阻断心脏H2受体所需剂量的西咪替丁，可能通过增加内向Ca++电流介导而具有心脏刺激作用。
