Cardioprotective effects of the aminopeptidase P inhibitor apstatin: studies on ischemia/reperfusion injury in the isolated rat heart.

Abstract

Aminopeptidase P and angiotensin-converting enzyme (ACE) are responsible for the metabolism of exogenously administered bradykinin in the coronary circulation of the rat. It has been shown that ACE inhibitors decrease cytosolic enzyme release from the ischemic rat heart and reduce reperfusion-induced ventricular arrhythmias by increasing endogenous levels of bradykinin. It was hypothesized that the aminopeptidase P inhibitor apstatin could do the same. In an isolated perfused rat heart preparation subjected to global ischemia and reperfusion, both apstatin and ramiprilat (an ACE inhibitor) significantly decreased creatine kinase (CK) and lactate dehydrogenase (LDH) release. The difference between the postischemia and preischemia levels of released CK was reduced 68% by apstatin and 68% by ramiprilat compared with control. The corresponding reductions in LDH release were 74% for apstatin and 81% for ramiprilat. A combination of the inhibitors was not significantly better than either one alone. Apstatin and ramiprilat also significantly reduced the duration of reperfusion-induced ventricular fibrillation by 69 and 61%, respectively. The antiarrhythmic effect of apstatin was reversed by HOE140, a bradykinin B2-receptor antagonist, suggesting that apstatin is acting by potentiating endogenously formed bradykinin. The results demonstrate that the aminopeptidase P inhibitor apstatin is cardioprotective in this model of cardiac ischemia/ reperfusion injury.

• Authors: C Erşahin, D E Euler, W H Simmons
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 34 Issue 4 Pg. 604-11 (Oct 1999) ISSN: 0160-2446 [Print] United States
• PMID: 10511138 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic beta-Antagonists
• Angiotensin-Converting Enzyme Inhibitors
• Cardiovascular Agents
• Peptides
• Protease Inhibitors
• ramiprilat
• icatibant
• L-Lactate Dehydrogenase
• Creatine Kinase
• apstatin
• Ramipril
• Bradykinin

Topics

• Adrenergic beta-Antagonists (pharmacology)
• Angiotensin-Converting Enzyme Inhibitors (pharmacology)
• Animals
• Arrhythmias, Cardiac (pathology)
• Bradykinin (analogs & derivatives, pharmacology)
• Cardiovascular Agents (pharmacology)
• Creatine Kinase (metabolism)
• Drug Interactions
• In Vitro Techniques
• L-Lactate Dehydrogenase (metabolism)
• Male
• Peptides (pharmacology)
• Perfusion
• Protease Inhibitors (pharmacology)
• Ramipril (analogs & derivatives, pharmacology)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (pathology)
• Ventricular Fibrillation (pathology)