Cyclooxygenase mediates cardioprotection of angiotensin-(1-7) against ischemia/reperfusion-induced injury through the inhibition of oxidative stress

• Published in: Molecular medicine reports Vol. 4; no. 6; pp. 1145 - 1150
• Main Authors: Liao, Xinxue, Wang, Lichun, Yang, Chuntao, He, Jiangui, Wang, Xiuyu, Guo, Ruixian, Lan, Aiping, Dong, Xiaobian, Yang, Zhanli, Wang, Huaqiao, Feng, Jianqiang, Ma, Hong
• Format: Journal Article
• Language: English
• Published: Greece 01.11.2011
• Subjects: Angiotensin I - pharmacology; Animals; Apoptosis - drug effects; Arrhythmias, Cardiac - prevention & control; Blood Pressure - physiology; Cardiotonic Agents - pharmacology; Cyclooxygenase Inhibitors - pharmacology; Indomethacin - pharmacology; Male; Malondialdehyde - metabolism; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - prevention & control; Oxidative Stress - drug effects; Peptide Fragments - pharmacology; Prostaglandin-Endoperoxide Synthases - metabolism; Rats; Superoxide Dismutase - metabolism; Ventricular Function - physiology
• ISSN: 1791-2997; 1791-3004
• DOI: 10.3892/mmr.2011.570

Angiotensin (Ang)-(1-7) exhibits cardioprotective effects in myocardial ischemia reperfusion (I/‌R)-induced injury. However, the roles of oxidation and cyclooxygenase (COX) in the cardioprotection of Ang-(1-7) remain unclear. This study was conducted to investigate whether oxidation and COX were involved in the cardioprotection of Ang-(1-7) against I/‌R-induced injury in isolated rat hearts. The hearts were subjected to 15 min regional ischemia followed by 30 min reperfusion. Myocardial I/‌R treatment induced significant cardiac dysfunction, including ventricular arrhythmia (VA) and a reduction of left ventricular systolic pressure (LVSP), cardiomyocyte apoptosis and oxidative stress, manifesting as an increase in malondialdehyde (MDA) production and a decrease in superoxide dismutase (SOD) activity. Pretreatment of the hearts with 1.0 nmol/‌l Ang-(1-7) for 30 min prior to ischemia considerably attenuated I/‌R-induced VA, apoptosis and MDA production, and enhanced LVSP and SOD activity. These cardioprotective effects of Ang-(1-7) were antagonized by the intraperitoneal injection of 5 mg/‌kg body weight indomethacin (IDM, a COX inhibitor), presenting as an enhancement of VA, apoptosis and MDA production as well as a reduction of LVSP and SOD activity. In conclusion, COX mediated Ang-(1-7)-induced cardioprotection via its antioxidative mechanism.