Cardioprotective effects of angiotensin III against ischemic injury via the AT2 receptor and KATP channels

Physiological Reports

Byung Mun Park¹  Shan Gao¹  Seung Ah Cha¹  Byung Hyun Park² 

[1] Department of Physiology, Research Institute for Endocrine Sciences, Chonbuk National University Medical School, Jeonju, Korea;Department of Biochemistry, Research Institute for Endocrine Sciences, Chonbuk National University Medical School, Jeonju, Korea

关键词: Angiotensin III;    apoptosis;    atrial natriuretic peptide;    Bax;    Bcl‐2;    caspase‐3;    caspase‐9;    catalase;    heart;    heme oxygenase‐1;    ischemia;    KATP channel;    superoxide dismutase;   

DOI  :  10.1002/phy2.151

来源: Wiley

【 摘 要 】

Abstract

Angiotensin III (Ang III) has similar effects on blood pressure and aldosterone secretion as Ang II, but cardioprotective effects are also proposed. In this study, we investigated whether Ang III protects the heart against ischemia/reperfusion (I/R) injury. After sacrificing Sprague-Dawley rats, the hearts were perfused with Krebs–Henseleit buffer for a 20 min preischemic period with and without Ang III followed by 20-min global ischemia and 50-min reperfusion. Pretreatment with Ang III (1 μmol/L) improved an increased postischemic left ventricular end-diastolic pressure (LVEDP) and a decreased postischemic left ventricular developed pressure (LVDP) induced by reperfusion compared to untreated hearts. Ang III markedly decreased infarct size and lactate dehydrogenase levels in effluent during reperfusion. Ang III increased coronary flow and the concentrations of atrial natriuretic peptide in coronary effluent during reperfusion. Pretreatment with Ang II type 2 receptor (AT₂R) antagonist or ATP-sensitive K⁺ channel (K_ATP) blocker for 15 min before ischemia attenuated the improvement of LVEDP, LVDP, and ±dP/dt induced by Ang III. Ang III treatment increased Mn-superoxide dismutase, catalase, and heme oxygenase-1 protein levels, which was attenuated by pretreatment with AT₂R antagonist or K_ATP blocker. Ang III treatment also decreased Bax, caspase-3, and caspase-9 protein levels, and increased Bcl-2 protein level, which were attenuated by pretreatment with AT₂R antagonist or K_ATP blocker. These results suggest that the cardioprotective effects of Ang III against I/R injury may be partly related to activating antioxidant and antiapoptotic enzymes via AT₂R and K_ATP channels.

【 授权许可】

CC BY   
© 2013 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

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