Enhanced expression and activity of xanthine oxidoreductase in the failingheart

The molecular basis for heart failure is unknown, but oxidative stress is a ssociated with the pathogenesis of the disease. We tested the hypothesis th at the activity of xanthine oxidoreductase (XOR)*, a free-radical generatin g enzyme, increases in hypertrophied and failing heart. We studied XOR in t wo rat models: (1) The monocrotaline-induced right ventricular hypertrophy and failure model; (2) coronary artery ligation induced heart failure, with left ventricular failure and compensatory right ventricular hypertrophy at different stages at 3 and 8 weeks post-infarction, respectively. XOR activ ity was measured at 30 degreesC and the reaction products were analysed by HPLC. In both models XOR activity in hypertrophic and control ventricles wa s similar. In the monocrotaline model, the hearts showed enhanced XOR activ ity in the failing right ventricle (65 +/- 5 mU/g w/w), as compared to that in the unaffected left ventricle (47 +/- 3 mU/g: P<0.05, n = 6-7). In the coronary ligation model, XOR activities did not differ at 3 and 8 weeks. In the infarct ed left ventricle, XOR activity increased from 29.4 +/- 1.4 mU /g (n = 6) in sham-operated rats, to 48 +/- 3 and 80 +/- 6 mU/g (n = 8; P<. 05 v sham) in the viable and infarcted parts of failing rat hearts, respect ively. With affinity-purified polyclonal antibody, XOR was localized in CD6 8 + inflammatory cells of which the number increased more in the failing th an in sham-operated hearts. Our results show that the expression of functio nal XOR is elevated in failing but not in hypertrophic ventricles, suggesti ng its potential role in the transition from cardiac hypertrophy into failu re. (C) 2000 Academic Press.