Effects of lisinopril on electromechanical properties and membrane currents in guinea-pig cardiac preparations.
1. The effects of the angiotensin-converting enzyme inhibitor, lisinopril, were studied in guinea-pig atria and papillary muscles and in single isolated ventricular cells. 2. In isolated right atria, lisinopril (0.001-10 microM) decreased the amplitude and rate of the spontaneous contractions. 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 electrophysiological characteristics of the ventricular action potentials recorded in papillary muscles perfused with normal Tyrode solution or elicited by isoprenaline in papillary muscles perfused with 27 mM K Tyrode solution. 4. In single ventricular cells, lisinopril (10 microM) had no effect on the inward L-type Ca2+ (ICa,L), the inward rectifier (IK1) or the delayed rectifier K+ currents (IK). However, it abolished the stimulation-dependent facilitation of the L-type Ca2+ current. 6. These results indicate that the negative inotropic effect of lisinopril cannot 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.
Valenzuela
C
C
Department of Pharmacology, School of Medicine, Universidad Complutense, Madrid, Spain.
Pérez
O
O
Casis
O
O
Duarte
J
J
Pérez-Vizcaino
F
F
Delpón
E
E
Tamargo
J
J
D000200:Action Potentials / Q000187:drug effects; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004151:Dipeptides / Q000494:pharmacology*; D004594:Electrophysiology; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000166:cytology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D017706:Lisinopril; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010210:Papillary Muscles / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D015220:Calcium Channels; D004151:Dipeptides; D007473:Ion Channels; D015221:Potassium Channels; D017706:Lisinopril