Dose-response studies with Idrapril (cas 127420-24-0) in the rat heart during acute myocardial ischaemia and reperfusion

Add time:08/07/2019    Source:sciencedirect.com

We assessed the effects of Idrapril (cas 127420-24-0), 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 μg/ml), captopril (80 μg/ml) or vehicle were given before ischaemia and throughout reperfusion. Post-ischaemic recovery of coronary flow was significantly decreased with 50 μg/ml of idrapril (43 ± 9% compared to 64 ± 3% in controls) whereas heart rate was unaffected. Recovery of developed pressure and activity of cardiac angiotenδin-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.

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