CARDIOPROTECTIVE EFFECT OF THE ANGIOTENSIN-II TYPE-1 RECEPTOR ANTAGONIST TCV-116 ON ISCHEMIA-REPERFUSION INJURY

We investigated the protective effect of angiotensin H (Ang II) type 1 receptor antagonist on myocardial ischemia-reperfusion injury and the role of exogenous Ang II to this injury in perfused hearts. We orally administered TCV-116 (Ang II type 1 receptor antagonist) and delapril (angiotesin converting enzyme inhibitor) to Wistar rats for 1 week an d measured the. immunoreactive cardiac Ang II. Immunoreactive cardiac Ang II (pg/gm tissue) was 14.3 +/- 2.0 in control group, 11.8 +/- 0.8 in TCV-116-treated group, and 7.3 +/- 0.6 in delapril-treated group (p < 0.05 compared to TCV-116-treated group; p < 0.01 compared to contro l group). The 15 hearts (five rats in each group) were perfused by a L angendorff method and global ischemia was maintained for 30 min. Both TCV-116 and delapril were found to improve postischemic cardiac functi on and decrease reperfusion creatine kinase (CK) release. Ang II injec tion before ischemia worsened postischemic cardiac function and increa sed reperfusion CK release. Only TCV-116 prevented this injury. These data indicated that TCV-116 Ang II type 1 receptor antagonist was effe ctive against myocardial ischemia-reperfusion injury, and exogenous An g II accerelated this injury through Ang II type 1 receptor.