EFFECTS OF LISINOPRIL ON ELECTROMECHANICAL PROPERTIES AND MEMBRANE CURRENTS IN GUINEA-PIG CARDIAC PREPARATIONS

1 The effects of the angiotensin-converting enzyme inhibitor, lisinopr il, were studied in guinea-pig atria and papillary muscles and in sing le isolated ventricular cells. 2 In isolated right atria, lisinopril ( 0.001 - 10 mum) decreased the amplitude and rate of the spontaneous co ntractions. In electrically driven left atria this negative inotropic effect was accompanied by a shortening of the time to peak tension and time for total contraction. 3 Lisinopril did not modify the electroph ysiological characteristics of the ventricular action potentials recor ded in papillary muscles perfused with normal Tyrode solution or elici ted by isoprenaline in papillary muscles perfused with 27 mm K Tyrode solution. 4 In single ventricular cells, lisinopril (10 mum) had no ef fect on the inward L-type Ca2+ (I(Ca,L)), the inward rectifier (I(K1)) or the delayed rectifier K+ currents (I(K)). However, it abolished th e stimulation-dependent facilitation of the L-type Ca2+ current. 6 The se results indicate that the negative inotropic effect of lisinopril c annot be explained by a decrease in Ca2+ entry through L-type channels and suggest that lisinopril may possibly act at an intracellular site to reduce contractile force.