title: Cyclooxygenase mediates cardioprotection of angiotensin-(1-7) against ischemia/reperfusion-induced injury through the inhibition of oxidative stress.
abstract: 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.
authors.affiliation: Department of Cardiovasology, Hypertension and Vascular Diseases, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, PR China.
authors.forename: Xinxue
authors.initials: X
authors.lastname: Liao
authors.forename: Lichun
authors.initials: L
authors.lastname: Wang
authors.forename: Chuntao
authors.initials: C
authors.lastname: Yang
authors.forename: Jiangui
authors.initials: J
authors.lastname: He
authors.forename: Xiuyu
authors.initials: X
authors.lastname: Wang
authors.forename: Ruixian
authors.initials: R
authors.lastname: Guo
authors.forename: Aiping
authors.initials: A
authors.lastname: Lan
authors.forename: Xiaobian
authors.initials: X
authors.lastname: Dong
authors.forename: Zhanli
authors.initials: Z
authors.lastname: Yang
authors.forename: Huaqiao
authors.initials: H
authors.lastname: Wang
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Feng
authors.forename: Hong
authors.initials: H
authors.lastname: Ma
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001145:Arrhythmias, Cardiac / Q000517:prevention & control; D001794:Blood Pressure / Q000502:physiology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism; D016276:Ventricular Function / Q000502:physiology
chemical_list: D002316:Cardiotonic Agents; D016861:Cyclooxygenase Inhibitors; D010446:Peptide Fragments; D008315:Malondialdehyde; D000803:Angiotensin I; D011451:Prostaglandin-Endoperoxide Synthases; D013482:Superoxide Dismutase; C118790:angiotensin I (1-7); D007213:Indomethacin