Attenuation of renal excretory responses to ANG II during inhibition of superoxide dismutase in anesthetized rats

作者：Khan Md Abdul Hye; Islam Mohammed Toriqul; Castillo Alexander; Majid Dewan Syed Abdul^*

来源：American Journal of Physiology - Renal Fluid and Electrolyte Physiology, 2010, 298(2): F401-F407.

DOI：10.1152/ajprenal.00511.2009

• superoxide dismutase
• NADPH oxidase
• diethyldithiocarbamate
• renal hemodynamics
• sodium excretion

Khan MA, Islam MT, Castillo A, Majid DS. Attenuation of renal excretory responses to ANG II during inhibition of superoxide dismutase in anesthetized rats. Am J Physiol Renal Physiol 298: F401-F407, 2010. First published November 18, 2009; doi: 10.1152/ajprenal.00511.2009.-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 mu g.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 mu M) 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.

• 出版日期2010-2