Ethanol Extract of Lycopus lucidus Elicits Positive Inotropic Effect Via Activation of Ca2+ Entry and Ca2+ Release in Beating Rabbit Atria

Lycopus lucidus Turcz has been widely used as a traditional Oriental medicine (TOM) in Korea and China and prescribed for the enhancement of heart function. However, the precise effects have yet to be defined. The purpose of the present study was, therefore, to address whether the ethanol extract of Lycopus lucidus Turcz (ELT) has a positive inotropic effect. ELT-induced changes in atrial mechanical dynamics (pulse pressure, dp/dt, and stroke volume), and cAMP efflux were measured in perfused beating rabbit atria. Three active components, rosmarinic acid, betulinic acid, and oleanolic acid were identified in ELT by high performance liquid chromatography analysis. ELT increased atrial dynamics in a concentration-dependent manner without changes in atrial cAMP levels and cAMP efflux. The ELT-induced positive inotropic effect was blocked by inhibition of the L-type Ca2+ channels and sarcoplasmic reticulum (SR). Inhibitors of beta-adrenoceptors had no effect on the ELT-induced positive inotropic effect. The results suggest that ELT exerts a positive inotropic effect via activation of Ca2+ entry through L-type Ca2+ channel and Ca2+ release from the SR in beating rabbit atria.