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Effect of the angiotensin-converting enzyme inhibitor, perindoprilat, and of angiotensin-II on the transient inward current of rabbit ventricular myocytes

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Summary

Angiotensin-converting enzyme (ACE) inhibitors protect the myocardium from experimental lethal ventricular arrhythmias induced by ischemia or reperfusion. Hypothetically, such arrhythmias may result from the calcium-dependent transient inward current Iti. It is already known that perindoprilat decreased the transient inward current in guinea-pig myocytes [1]. In the same preparation, however, angiotensin-IIdecreased the transient inward current, an effect opposite to that required to prove that the ACE inhibitor exerted its beneficial effects on Iti by lessening the action of angiotensin-II. We, therefore, selected another species, the rabbit, in which angiotensin-II was known to have a positive inotropic effect. Perindoprilat (1 µM but not 0.01 µM) decreased the transient inward current from −8.93±0.80 µA/cm2 to −5.33±0.74 µA/cm2 (p<0.05). Perindoprilat (1 µM) also protected from the effects of angiotensin-II (0.01 and 0.1 µM), which on its own increased the amplitude of the transient inward current. Based on our results, we conclude that perindoprilat (1 µM) prevents the effect of angiotensin-II in promoting the transient inward current in the rabbit. Hence our data support the hypothesis that the ACE inhibitor, perindoprilat, might in relatively high concentrations have an antiarrhythmic effect, at least in part through inhibition of angiotensin-II-evoked calcium-dependent Iti.

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Authors and Affiliations

  1. Medical Research Council Ischaemic Heart Disease Research Unit, University of Cape Town Medical School, Observatory 7925, Cape Town, South Africa

    R. Enous &  L. H. Opie

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  1. R. Enous
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  2. L. H. Opie
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This article was evaluated by the San Francisco Editorial Office by two anonymous referees.

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Enous, R., Opie, L.H. Effect of the angiotensin-converting enzyme inhibitor, perindoprilat, and of angiotensin-II on the transient inward current of rabbit ventricular myocytes. Cardiovasc Drug Ther 8, 647–651 (1994). https://doi.org/10.1007/BF00877418

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  • DOI: https://doi.org/10.1007/BF00877418

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