Abstract
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.
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Selected References
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- Bach R., Zardini P. Long-acting angiotensin-converting enzyme inhibition: once-daily lisinopril versus twice-daily captopril in mild-to-moderate heart failure. Am J Cardiol. 1992 Oct 8;70(10):70C–77C. doi: 10.1016/0002-9149(92)91361-7. [DOI] [PubMed] [Google Scholar]
- Braunwald E. ACE inhibitors--a cornerstone of the treatment of heart failure. N Engl J Med. 1991 Aug 1;325(5):351–353. doi: 10.1056/NEJM199108013250508. [DOI] [PubMed] [Google Scholar]
- Bryant S. M., Ryder K. O., Hart G. Effects of captopril on membrane current and contraction in single ventricular myocytes from guinea-pig. Br J Pharmacol. 1991 Feb;102(2):462–466. doi: 10.1111/j.1476-5381.1991.tb12195.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Case D. E. The clinical pharmacology of lisinopril. J Hum Hypertens. 1989 Jun;3 (Suppl 1):127–131. [PubMed] [Google Scholar]
- Delpón E., Tamargo J., Sánchez-Chapula J. Further characterization of the effects of imipramine on plateau membrane currents in guinea-pig ventricular myocytes. Naunyn Schmiedebergs Arch Pharmacol. 1991 Dec;344(6):645–652. doi: 10.1007/BF00174748. [DOI] [PubMed] [Google Scholar]
- Delpón E., Valenzuela C., Pérez O., Tamargo J. Electrophysiological effects of CRE-1087 in guinea-pig ventricular muscles. Br J Pharmacol. 1992 Oct;107(2):515–520. doi: 10.1111/j.1476-5381.1992.tb12776.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Delpón E., Valenzuela C., Tamargo J. Electrophysiological effects of E-3753, a new antiarrhythmic drug, in guinea-pig ventricular muscle. Br J Pharmacol. 1989 Apr;96(4):970–976. doi: 10.1111/j.1476-5381.1989.tb11909.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Delpón E., Valenzuela C., Tamargo J. Electrophysiological effects of the combination of mexiletine and flecainide in guinea-pig ventricular fibres. Br J Pharmacol. 1991 Jun;103(2):1411–1416. doi: 10.1111/j.1476-5381.1991.tb09803.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Diez J., Tamargo J., Valenzuela C. Negative inotropic effect of somatostatin in guinea-pig atrial fibres. Br J Pharmacol. 1985 Nov;86(3):547–555. doi: 10.1111/j.1476-5381.1985.tb08930.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fedida D., Noble D., Spindler A. J. Mechanism of the use dependence of Ca2+ current in guinea-pig myocytes. J Physiol. 1988 Nov;405:461–475. doi: 10.1113/jphysiol.1988.sp017342. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
- Horn R., Marty A. Muscarinic activation of ionic currents measured by a new whole-cell recording method. J Gen Physiol. 1988 Aug;92(2):145–159. doi: 10.1085/jgp.92.2.145. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Isenberg G., Klöckner U. Calcium currents of isolated bovine ventricular myocytes are fast and of large amplitude. Pflugers Arch. 1982 Oct;395(1):30–41. doi: 10.1007/BF00584965. [DOI] [PubMed] [Google Scholar]
- Kiyosue T., Arita M. Late sodium current and its contribution to action potential configuration in guinea pig ventricular myocytes. Circ Res. 1989 Feb;64(2):389–397. doi: 10.1161/01.res.64.2.389. [DOI] [PubMed] [Google Scholar]
- Kurachi Y., Asano Y., Takikawa R., Sugimoto T. Cardiac Ca current does not run down and is very sensitive to isoprenaline in the nystatin-method of whole cell recording. Naunyn Schmiedebergs Arch Pharmacol. 1989 Aug;340(2):219–222. doi: 10.1007/BF00168972. [DOI] [PubMed] [Google Scholar]
- Lancaster S. G., Todd P. A. Lisinopril. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension and congestive heart failure. Drugs. 1988 Jun;35(6):646–669. doi: 10.2165/00003495-198835060-00003. [DOI] [PubMed] [Google Scholar]
- Lee K. S. Potentiation of the calcium-channel currents of internally perfused mammalian heart cells by repetitive depolarization. Proc Natl Acad Sci U S A. 1987 Jun;84(11):3941–3945. doi: 10.1073/pnas.84.11.3941. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Malécot C. O., Trautwein W. On the relationship between V max of slow responses and Ca-current availability in whole-cell clamped guinea pig heart cells. Pflugers Arch. 1987 Sep;410(1-2):15–22. doi: 10.1007/BF00581890. [DOI] [PubMed] [Google Scholar]
- Matsuura H., Ehara T., Imoto Y. An analysis of the delayed outward current in single ventricular cells of the guinea-pig. Pflugers Arch. 1987 Dec;410(6):596–603. doi: 10.1007/BF00581319. [DOI] [PubMed] [Google Scholar]
- Mitra R., Morad M. Two types of calcium channels in guinea pig ventricular myocytes. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5340–5344. doi: 10.1073/pnas.83.14.5340. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pfeffer J. M., Pfeffer M. A., Braunwald E. Influence of chronic captopril therapy on the infarcted left ventricle of the rat. Circ Res. 1985 Jul;57(1):84–95. doi: 10.1161/01.res.57.1.84. [DOI] [PubMed] [Google Scholar]
- Pérez-Vizcaino F., Carrón R., Delpón E., Tamargo J. Effects of (S)-nafenodone, a new antidepressant, in isolated guinea-pig atrial and ventricular muscle fibres. Eur J Pharmacol. 1991 Jun 18;199(1):43–50. doi: 10.1016/0014-2999(91)90635-4. [DOI] [PubMed] [Google Scholar]
- Sweet C. S., Emmert S. E., Stabilito I. I., Ribeiro L. G. Increased survival in rats with congestive heart failure treated with enalapril. J Cardiovasc Pharmacol. 1987 Dec;10(6):636–642. doi: 10.1097/00005344-198712000-00005. [DOI] [PubMed] [Google Scholar]
- Tseng G. N. Calcium current restitution in mammalian ventricular myocytes is modulated by intracellular calcium. Circ Res. 1988 Aug;63(2):468–482. doi: 10.1161/01.res.63.2.468. [DOI] [PubMed] [Google Scholar]
- Tsien R. W., Bean B. P., Hess P., Lansman J. B., Nilius B., Nowycky M. C. Mechanisms of calcium channel modulation by beta-adrenergic agents and dihydropyridine calcium agonists. J Mol Cell Cardiol. 1986 Jul;18(7):691–710. doi: 10.1016/s0022-2828(86)80941-5. [DOI] [PubMed] [Google Scholar]
- Valenzuela C., Bennett P. B. Voltage- and use-dependent modulation of calcium channel current in guinea pig ventricular cells by amiodarone and des-oxo-amiodarone. J Cardiovasc Pharmacol. 1991 Jun;17(6):894–902. doi: 10.1097/00005344-199106000-00006. [DOI] [PubMed] [Google Scholar]
- Valenzuela C., Delpón E., Tamargo J. Tonic and phasic Vmax block induced by 5-hydroxypropafenone in guinea pig ventricular muscles. J Cardiovasc Pharmacol. 1988 Oct;12(4):423–431. doi: 10.1097/00005344-198810000-00007. [DOI] [PubMed] [Google Scholar]
- Wallenstein S., Zucker C. L., Fleiss J. L. Some statistical methods useful in circulation research. Circ Res. 1980 Jul;47(1):1–9. doi: 10.1161/01.res.47.1.1. [DOI] [PubMed] [Google Scholar]
- Zannad F., van den Broek S. A., Bory M. Comparison of treatment with lisinopril versus enalapril for congestive heart failure. Am J Cardiol. 1992 Oct 8;70(10):78C–83C. doi: 10.1016/0002-9149(92)91362-8. [DOI] [PubMed] [Google Scholar]
- Zygmunt A. C., Maylie J. Stimulation-dependent facilitation of the high threshold calcium current in guinea-pig ventricular myocytes. J Physiol. 1990 Sep;428:653–671. doi: 10.1113/jphysiol.1990.sp018233. [DOI] [PMC free article] [PubMed] [Google Scholar]
