Angiotensin II-NAD(P)H oxidase-stimulated superoxide modifies tubulovascular nitric oxide cross-talk in renal outer medulla

Takefumi Mori, Allen W. Cowley

Research output: Contribution to journalArticlepeer-review

84 Citations (Scopus)

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 μmol/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 O 2.- 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 O 2.- 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.

Original languageEnglish
Pages (from-to)588-593
Number of pages6
JournalHypertension
Volume42
Issue number4 I
DOIs
Publication statusPublished - 2003 Oct 1

Keywords

  • Angiotensin II
  • Free radicals
  • Oxidative stress
  • Rats
  • Renal blood flow

ASJC Scopus subject areas

  • Internal Medicine

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