Faculty Collaboration Database

Angiotensin II-NAD(P)H oxidase-stimulated superoxide modifies tubulovascular nitric oxide cross-talk in renal outer medulla. Hypertension 2003 Oct;42(4):588-93

Date

09/17/2003

Pubmed ID

12975384

DOI

10.1161/01.HYP.0000091821.39824.09

Scopus ID

2-s2.0-0141893554 (requires institutional sign-in at Scopus site)   89 Citations

Abstract

The source of superoxide (O2*-) production and cell-to-cell interactions of O2*- and nitric oxide (NO) in response to angiotensin II (AngII) were studied by fluorescence microscopic techniques to image rat renal outer medullary microtissue strips. Changes in intracellular O2*- were determined by dihydroethidium-ethidium ratios, and NO was determined with 4,5-diaminofluorescein diacetate. AngII (1 micromol/L) significantly increased O2*- in the isolated, medullary thick ascending limb (mTAL). These responses were inhibited by the superoxide dismutase mimetic 4-hydroxytetramethylpiperidine-1-oxyl (TEMPOL) and by the NAD(P)H oxidase inhibitors diphenylene iodonium and apocynin. AngII did not increase O2*- in either pericytes of isolated, intact vasa recta (VR) or pericytes of VR with a disrupted endothelium, even when surrounded by mTAL. However, AngII did increase O2*- when the tissue strips were preincubated with the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), indicating that cross-talk of O2*- from mTAL to the VR occurred but was normally inhibited by NO. Also, tissue O2*- reduction by TEMPOL increased the diffusion of NO from mTAL to the pericytes, indicating that cross-talk of NO from the mTAL to the VR is also inhibited by O2*-. We conclude that AngII stimulates O2*- production in mTAL via the NAD(P)H oxidase pathway and that interactions of O2*- and NO ultimately determine the effectiveness of in situ free-radical cross-talk between the mTAL and the VR.

Author List

Mori T, 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

Angiotensin II
Animals
Culture Techniques
Epithelial Cells
Kidney Medulla
Kidney Tubules, Distal
NADH, NADPH Oxidoreductases
NADPH Oxidases
Nitric Oxide
Paracrine Communication
Pericytes
Rats
Rats, Sprague-Dawley
Superoxides