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 (KATP) 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 KATP 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 KATP 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
KATP channels.