Molecular mechanisms and therapeutic strategies of chronic renal injury: Physiological role of angiotensin II-induced oxidative stress in renal medulla

Takefumi Mori, Allen W. Cowley, Sadayoshi Ito

Research output: Contribution to journalShort survey

41 Citations (Scopus)

Abstract

Renal medullary circulation has now been found to play a fundamental role in regulating long-term blood pressure control and fluid balance. Elevation of superoxide or reduction of nitric oxide (NO) in renal medulla decreases medullary blood flow and Na excretion, resulting in sustained hypertension. Angiotensin II (Ang II)-induced interaction of superoxide and NO was determined in thin tissue strips isolated from the renal outer medullary region of Sprague-Dawley rats using fluorescent microscopy techniques. Ang II can induce diffusion of NO, but not superoxide, from the medullary thick ascending limb (mTAL) to the surrounded vasa recta. However, when NO is reduced by the NO scavenger carboxy-PTIO, Ang II can induce superoxide diffusion from mTAL to vasa recta pericytes. Therefore, the physiological action of oxidative stress in renal medullary region is demonstrated as balance of superoxide and NO diffusion ("tubulo-vascular cross-talk"). These results explain how chronically hypoxic medulla can maintain blood flow. In other studies using chronically instrumented rats, we found that nearly 70% of Ang II-induced medullary renal injury was dependent on pressure determined by servo-control of renal perfusion pressure, whereas 30% of the injury was non-hemodynamic. We conclude that oxidative stress within the renal medulla can induce hypertension and also make the kidney functionally more vulnerable to the effects of Ang II.

Original languageEnglish
Pages (from-to)2-8
Number of pages7
JournalJournal of Pharmacological Sciences
Volume100
Issue number1
DOIs
Publication statusPublished - 2006 Feb 6

Keywords

  • Angiotensin II
  • Hypertension
  • Oxidative stress
  • Reactive oxygen species
  • Renal injury

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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