| Abstrakt: |
To examine the functional interaction between superoxide dismutase (SOD) and NADPH oxidase activity, we assessed renal responses to acute intra-arterial infusion of ANG 11(0.5 ng·kg-1·min-1) before and during administration of a SOD inhibitor, diethyldithiocarbamate (DETC, 0.5 ng·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 tis- sue 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 (UNaV) as reported previously. Before DETC, ANG U infusion decreased RBF (-18 ± 3%), CBF (-16 ± 3%), MBF [-5 ± 6%; P = not significant (NS)I, GFR (-31 ± 4%), V (-34 ± 2%), and UNaV (-53 ± 3%). During DETC infusion, ANG H 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%; UNaV; -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 IT-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. [ABSTRACT FROM AUTHOR] |
