ELECTROMECHANICAL EFFECTS OF EVODIAMINE IN GUINEA-PIG CARDIAC TISSUES

Effects of evodiamine on the action potential and contractile force of guinea-pig heart tissues were studied in vitro. In sinoatrial tissues, 0.1-1 mu M evodiamine accelerated the spontaneous rhythms and increased the contractile force. At the highest concentration (30 mu M), however, evodiamine slowed the spontaneous rate and significantly decreased the force. The positive chronotropic and inotropic effects were markedly diminished by pretreating the tissues with 3.4 mu M propranolol and were completely abolished by additional blocking agents (1 mu M phentolamine, cimetidine and pyrilamine). In ventricular papillary muscles driven at a constant rate, evodiamine (1-10 mu M) induced transient positive inotropic effect within 5 min exposure and then the force gradually declined. Propranolol prevented the initial increase in force induced by 1 mu M evodiamine as well as that induced by 10 mu M tyramine. The depressant effects of evodiamine occurred mainly at higher concentrations and were exaggerated under condition of calcium overload induced by cardiotonic agents. The present findings indicate that evodiamine induces indirect excitatory and direct depressant effects in isolated guinea-pig heart tissues. The excitatory effects may be mediated mainly through an activation of the beta-adrenoceptors in cardiac tissues.