Effects of lisinopril on cardiac contractility and ionic currents

1. The effects of lisinopril, an angiotensin-converting enzyme inhibitor, were studied on cardiac contractile force, action potential characteristics and membrane ionic currents. 2. In guinea-pig atria, lisinopril (0.001-1 microM) exerted a negative inotropic effect which was accompanied by a shortening of the time to peak tension and time for total contraction. However, it did not modify atrial rate or the characteristics of the ventricular action potentials recorded either in normally polarized or in depolarized papillary muscles. 3. In isolated guinea-pig ventricular myocytes, lisinopril had no effect on the inward L-type Ca2+ (ICa,L), the inward rectifier (IK1) or the delayed rectifier K+ currents (IK), but abolished the stimulation-dependent facilitation of the ICa,L. Furthermore, it did not alter a cloned human cardiac K+ current (hKv1.5) expressed in a mouse L cell line (Ltk-). 4. The absence of negative inotropic effects in patients with congestive heart failure can be explained by the potent arterial vasodilator action of lisinopril which reduced left ventricular afterload overriding the expected direct cardiodepressant effects of the drug.