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

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 I_ti. 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 I_ti 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 I_ti.This article was evaluated by the San Francisco Editorial Office by two anonymous referees.