Faculty Collaboration Database

Production and actions of superoxide in the renal medulla. Hypertension 2001 Feb;37(2 Pt 2):547-53

Date

03/07/2001

Pubmed ID

11230333

DOI

10.1161/01.hyp.37.2.547

Scopus ID

2-s2.0-0035097458 (requires institutional sign-in at Scopus site)   276 Citations

Abstract

The present study characterized the biochemical pathways responsible for superoxide (O(2)(-.)) production in different regions of the rat kidney and determined the role of O(2)(-.)in the control of renal medullary blood flow (MBF) and renal function. By use of dihydroethidium/DNA fluorescence spectrometry with microtiter plates, the production of O(2)(-. )was monitored when tissue homogenate from different kidney regions was incubated with substrates for the major O(2)(-.)-producing enzymes, such as NADH/NADPH oxidase, xanthine oxidase, and mitochondrial respiratory chain enzymes. The production of O(2)(-. )via NADH oxidase was greater (P<0.05) in the renal cortex and outer medulla (OM) than in the papilla. The mitochondrial enzyme activity for O(2)(-.)production was higher (P<0.05) in the OM than in the cortex and papilla. Compared with NADH oxidase and mitochondrial enzymes, xanthine oxidase and NADPH oxidase produced much less O(2)(-. )in the kidney under this condition. Overall, the renal OM exhibited the greatest enzyme activities for O(2)(-.)production. In anesthetized rats, renal medullary interstitial infusion of a superoxide dismutase inhibitor, diethyldithiocarbamate, markedly decreased renal MBF and sodium excretion. Diethyldithiocarbamate (5 mg/kg per minute by renal medullary interstitial infusion [RI]) reduced the renal medullary laser-Doppler flow signal from 0.6+/-0.04 to 0.4+/-0.03 V, a reduction of 33%, and both urine flow and sodium excretion decreased by 49%. In contrast, a membrane-permeable superoxide dismutase mimetic, 4-hydroxytetramethyl-piperidine-1-oxyl (TEMPOL, 30 micromol/kg per minute RI) increased MBF and sodium excretion by 34% and 69%, respectively. These effects of TEMPOL on renal MBF and sodium excretion were not altered by pretreatment with N(G)-nitro-L-arginine methyl ester (10 microgram/kg per minute RI). We conclude that (1) renal medullary O(2)(-. )is primarily produced in the renal OM; (2) both NADH oxidase and mitochondrial enzymes are responsible for the O(2)(-.)production in this kidney region; and (3) O(2)(-. )exerts a tonic regulatory action on renal MBF.

Author List

Zou AP, Li N, Cowley AW Jr

Author

Allen W. Cowley Jr PhD Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cyclic N-Oxides
Ditiocarb
Electron Transport
Enzyme Inhibitors
Kidney Cortex
Kidney Medulla
Male
Multienzyme Complexes
NADH, NADPH Oxidoreductases
Natriuresis
Rats
Rats, Sprague-Dawley
Regional Blood Flow
Renal Circulation
Spectrometry, Fluorescence
Spin Labels
Superoxide Dismutase
Superoxides