CHRONIC TREATMENT WITH PROPRANOLOL INDUCES ANTIOXIDANT CHANGES AND PROTECTS AGAINST ISCHEMIA-REPERFUSION INJURY

The goal of this study was to examine whether chronic administration o f propranolol offers protection against ischemia-reperfusion injury an d whether it induces any change in the myocardial endogenous antioxida nt enzyme activities and their gene expression, Rats were treated with propranolol (10 mg/kg/day, i.p.) for either 6 or 18 days, Forty-eight h after the last propranolol injection, isolated hearts were subjected to 60 min of global ischemia and 40 min of reperfusion, Resting tensi on in the control and treated groups after ischemia was 385 +/- 30 and 150 +/- 15%; and upon reperfusion was 140 +/- 11 and 49 +/- 6%, respe ctively as compared to the pre-ischemic values, Recovery of the contra ctile function in globally ischemic hearts upon reperfusion was about 35% in the treated group as compared to about 16% in the control group at 10 and 20 min, A positive response to catecholamine was observed i n hearts from propranolol group (C, 3.41 +/- 0.36; epi, 6.03 +/- 0.47 g/g) and was comparable to control hearts (C, 3.55 +/- 0.31; epi, 6.48 +/- 0.42 g/g), Myocardial antioxidants, catalase and glutathione pero xidase enzyme activities, in the treated group, prior to ischemia-repe rfusion were increased by 67 +/- 9 and 45 +/- 11%, respectively, over those in controls, Superoxide dismutase activity did not show any chan ge. The mRNA expression for the three antioxidant enzymes did not chan ge in the hearts of the treated group as compared to control, Lipid pe roxidation, both before and after the ischemia-reperfusion episode, wa s significantly reduced in the propranolol-treated hearts compared to the control group, Hearts studied at the end of reperfusion showed no difference in enzyme activities between treated and control groups, Th ese data show that propranolol treatment of the animals protects again st ischemia-reperfusion injury in isolated hearts in the absence of be ta-blockade. Increased endogenous antioxidant enzyme activities due to propranolol treatment may have a role in this protection. (C) 1997 Ac ademic Press Limited.