Dose-response studies with idrapril in the rat heart during acute myocardial ischaemia and reperfusion

We assessed the effects of idrapril, a novel angiotensin-converting enzyme inhibitor, and captopril in the isolated rat heart after ischaemia and reperfusion and measured angiotensin-converting enzyme activity in myocardial tissue. Hearts were perfused and subjected to global ischaemia and reperfusion. Idrapril (0.1, 1, 10, and 50 micrograms/ml), captopril (80 micrograms/ml) or vehicle were given before ischaemia and throughout reperfusion. Post-ischaemic recovery of coronary flow was significantly decreased with 50 micrograms/ml of idrapril (43 +/- 9% compared to 64 +/- 3% in controls) whereas heart rate was unaffected. Recovery of developed pressure and activity of cardiac angiotensin-converting enzyme were significantly reduced by idrapril in a dose-dependent manner. This study suggests that protection or lack of protection by idrapril on recovery of contractile function seems to depend on the degree of inhibition of tissue angiotensin-converting enzyme activity in the setting of acute heart ischaemic insult. Our results suggest that while a certain degree of inhibition of angiotensin-converting enzyme in the heart is beneficial, marked tissue inhibition may be deleterious.