Open AccessCardioprotective effects of angiotensin III against ischemic injury via the AT 2 receptor and K ATP channels
Author(s) -
Park Byung Mun,
Gao Shan,
Cha Seung Ah,
Park Byung Hyun,
Kim Suhn Hee
Publication year - 2013
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.1002/phy2.151
Subject(s) - medicine , angiotensin ii , preload , endocrinology , lactate dehydrogenase , ischemia , candesartan , antagonist , chemistry , pharmacology , aldosterone , reperfusion injury , channel blocker , renin–angiotensin system , receptor , blood pressure , hemodynamics , biochemistry , enzyme , calcium
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 μ mol/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 (AT 2 R) antagonist or ATP‐sensitive K + channel (K ATP ) blocker for 15 min before ischemia attenuated the improvement of LVEDP, LVDP, and ± d P /d t induced by Ang III. Ang III treatment increased Mn‐superoxide dismutase, catalase, and heme oxygenase‐1 protein levels, which was attenuated by pretreatment with AT 2 R 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 AT 2 R 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 AT 2 R and K ATP channels.