RESEARCH A Cardiac nitric oxide synthases are elev

nd fu isms damaging. Survival pathways, on the other hand, can be Journal of Nutritional BiochemCardiovascular Research and Alternative Medicine, University of Wyom-ing, Laramie, WY 82071, USA.deficiency have not been elucidated. Because prior work has implicated altered nitric oxide (NO) metabolism in this altered function, we have examined this pathway in further detail. Male Sprague–Dawley rats were fed diets that were either Cu adequate (6 mg Cu/kg diet) or Cu deficient (b0.5 mg Cu/kg diet) for 5 weeks. Endothelial NO synthase (NOS) and inducible NOS (iNOS) protein expressions, as measured by Western blot analysis, were 58 % and 40 % higher, respectively, in Cu-deficient than in Cu-adequate rat hearts. Cardiac NOS activity, as measured by conversion of 3H-arginine to 3H-citrulline, was 130 % higher in Cu-deficient than in Cu-adequate rats. NFnB is a known transcription factor for iNOS. Activation of NFnB, determined by an ELISA for the p65 subunit, was found to be 33 % higher in Cu-deficient than in Cu-adequate rats. Coupled with prior evidence of elevated cardiac nitrate/nitrite production in Cu-deficient rats, these data suggest multiple pathways for enhanced NO production that may contribute to altered cardiac function under dietary Cu deficiency