Effect of the angiotensin-converting enzyme inhibitor, perindoprilat, and of angiotensin-II on the transient inward current of rabbit ventricular myocytes.
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-II decreased 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 microM but not 0.01 microM) decreased the transient inward current from -8.93 +/- 0.80 microA/cm2 to -5.33 +/- 0.74 microA/cm2 (p < 0.05). Perindoprilat (1 microM) also protected from the effects of angiotensin-II (0.01 and 0.1 microM), which on its own increased the amplitude of the transient inward current. Based on our results, we conclude that perindoprilat (1 microM) 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.
Enous
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Medical Research Council Ischaemic Heart Disease Research Unit, University of Cape Town Medical School, South Africa.
Opie
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D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004594:Electrophysiology; D006329:Heart Conduction System / Q000187:drug effects*; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects*; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology; D011817:Rabbits
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D000804:Angiotensin II; C053500:perindoprilat; D002118:Calcium