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Abstract To examine the functional interaction between superoxide dismutase (SOD) and NADPH oxidase activity, we assessed renal responses to acute intra-arterial infusion of ANG II (0.5 ng·kg −1 ·min −1 ) before and during administration of a SOD inhibitor, diethyldithiocarbamate (DETC, 0.5 mg·kg −1 ·min −1 ), in enalaprilat-pretreated (33 μg·kg −1 ·min −1 ) rats ( n = 11). Total (RBF) and regional (cortical, CBF; medullary; MBF) renal blood flows were determined by Transonic and laser-Doppler flowmetry, respectively. Renal cortical and medullary tissue NADPH oxidase activity in vitro was determined using the lucigenin-chemiluminescence method. DETC treatment alone resulted in decreases in RBF, CBF, MBF, glomerular filtration rate (GFR), urine flow (V), and sodium excretion (U Na V) as reported previously. Before DETC, ANG II infusion decreased RBF (−18 ± 3%), CBF (−16 ± 3%), MBF −5 ± 6%; P = not significant (NS), GFR (−31 ± 4%), V (−34 ± 2%), and U Na V (−53 ± 3%). During DETC infusion, ANG II also caused similar reductions in RBF (−20 ± 4%), CBF (−19 ± 3%), MBF (−2 ± 2; P = NS), and in GFR (−22 ± 7%), whereas renal excretory responses (V; −12 ± 2%; U Na V; −24 ± 4%) were significantly attenuated compared with those before DETC. In in vitro experiments, ANG II (100 μM) enhanced NADPH oxidase activity both in cortical 13,194 ± 1,651 vs. 20,914 ± 2,769 relative light units (RLU)/mg protein and in medullary (21,296 ± 2,244 vs. 30,597 ± 4,250 RLU/mg protein) tissue. Application of DETC (1 mM) reduced the basal levels and prevented ANG II-induced increases in NADPH oxidase activity in both tissues. These results demonstrate that renal excretory responses to acute ANG II administration are attenuated during SOD inhibition, which seems related to a downregulation of NADPH oxidase in the deficient condition of SOD activity. superoxide dismutase NADPH oxidase diethyldithiocarbamate renal hemodynamics sodium excretion Copyright © 2010 the American Physiological Society
AJP - Renal Physiology – The American Physiological Society
Published: Feb 1, 2010
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