The pharmacological effect of a Viscum album aqueous extract was evaluated on the Langendorff isolated and perfused heart model in normotense male guinea pig hearts. Coronary vascular resistance, left intraventricular pressure, nitric oxide release in the perfusion liquid, cyclic guanosine monophosphate production, and analysis of inducible and endothelial nitric oxide synthases expression by Western Blot in ventricular tissue were recorded in absence and presence of blockers and inhibitors, such as 3 microM gadolinium chloride, 100 microM N(omega)-nitro-L-arginine methyl ester and 10 microM 1H-[1,2,4]oxadiazolo[4,2-a]quinoxalin-1-one. V. album aqueous extract exerts a significant decrease in the coronary vascular resistance, which courses with significant increases in nitric oxide and cyclic guanosine monophosphate production. Analysis of the expression of both nitric oxide synthases revealed that this extract significantly induces the expression of both isoforms in guinea pig hearts. These effects were inhibited by the presence of blockers and inhibitors. The coronary vasodilation induced by the extract is mediated by the nitric oxide/soluble guanylyl cyclase pathway. In addition, this extract shows a positive inotropic effect which that is tyramine-mediated by means of beta1-adrenergic stimulation.