Protective effect of hypoxia on mechanical and metabolic changes induced by hydrogen peroxide in rat hearts

The effect of hypoxia (20% O2 for 5 min) on the hydrogen peroxide (H2O2)-induced myocardial change was studied in the Langendorff rat heart, which was perfused at a constant flow rate and driven electrically. H2O2 decreased the left ventricular developed pressure, increased the left ventricular end-diastolic pressure, and decreased the myocardial ATP level. These mechanical and metabolic alterations induced by H2O2 were less prominent in the hypoxia-reoxygenated heart than in the normoxic heart (i.e., hypoxia had a protective effect on the H2O2-induced change). Both 8-phenyltheophylline (8-PT), a nonselective adenosine-receptor antagonist, and glyburide (Gly), an inhibitor of the ATP-sensitive potassium (KATP) channel, significantly reduced the protective effect of hypoxia. The adenosine A1-receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DP-CPX) reduced the protective effect of hypoxia incompletely. Gly, 8-PT, and DPCPX did not affect the mechanical function and energy metabolism of the hypoxia-reoxygenated heart without H2O2. These results suggest that brief and mild hypoxia attenuates the H2O2-induced mechanical and metabolic changes and that the protective effect of hypoxia is probably mediated by activation of the adenosine receptors, which open the KATP channel.