Beneficial effects of angiotensin I converting enzyme inhibitor on post-ischemic contractile function of perfused rat heart.

Abstract

The present study was undertaken to determine whether trandolaprilat, an active form of angiotensin I converting enzyme (ACE) inhibitor, may improve ischemia/reperfusion-induced contractile dysfunction and metabolic derangement of isolated rat hearts. Ischemia (25 min) and subsequent 60-min reperfusion resulted in a small recovery of post-ischemic left ventricular developed pressure (LVDP), a sustained increase in left ventricular end-diastolic pressure, an increase in the release of creatine kinase and ATP metabolites from the perfused heart, and changes in myocardial sodium, potassium, calcium and magnesium contents. Treatment with 10-100 microM of trandolaprilat for the last 10 min of pre-ischemia recovered approximately 50-90% of pre-ischemic LVDP during reperfusion, whereas that with 30-100 microM of enalaprilat restored approximately 55-65% of the pre-ischemic LVDP. Treatment with either trandolaprilat or enalaprilat at these concentrations attenuated the release of creatine kinase and ATP metabolites into the perfusate during reperfusion. Treatment with 30 microM trandolaprilat suppressed ischemia/reperfusion-induced changes in myocardial ion content. Treatment with bradykinin during the last 10 min of pre-ischemia also resulted in a post-ischemic contractile recovery with a degree similar to that of the trandolaprilat-treated hearts. E4177, an AT1-antagonist, showed no effect on ischemia/reperfusion-induced changes in cardiac parameters. The enhancement of post-ischemic contractile recovery by the ACE inhibitor was abolished by treatment with either Hoechst 140, a bradykinin (BK2) antagonist, or diclofenac, a cyclooxygenase inhibitor. These results suggest that trandolaprilat is capable of attenuating ischemia/reperfusion injury of isolated perfused hearts and altered BK metabolism is, at least in part, involved in this effect.

• Authors: K Tanonaka, T Kamiyama, A Takezono, K Sakai, S Takeo
• Journal: Journal of molecular and cellular cardiology (J Mol Cell Cardiol) Vol. 28 Issue 8 Pg. 1659-70 (Aug 1996) ISSN: 0022-2828 [Print] England
• PMID: 8877776 (Publication Type: Journal Article)

Chemical References

• Angiotensin Receptor Antagonists
• Angiotensin-Converting Enzyme Inhibitors
• Bradykinin Receptor Antagonists
• Cations
• Indoles
• Adenosine Triphosphate
• Creatine Kinase
• Enalaprilat
• trandolaprilat
• Bradykinin

Topics

• Adenosine Triphosphate (metabolism)
• Analysis of Variance
• Angiotensin Receptor Antagonists
• Angiotensin-Converting Enzyme Inhibitors (therapeutic use)
• Animals
• Bradykinin (pharmacology)
• Bradykinin Receptor Antagonists
• Cations (metabolism)
• Creatine Kinase (metabolism)
• Enalaprilat (pharmacology)
• Indoles (therapeutic use)
• Male
• Myocardial Contraction (drug effects)
• Myocardial Reperfusion Injury (drug therapy)
• Rats
• Rats, Wistar
• Treatment Outcome