Increased renal medullary H2O2 leads to hypertension

Ayako Makino, Meredith M. Skelton, Ai Ping Zou, Allen W. Cowley

Research output: Contribution to journalArticle

109 Scopus citations

Abstract

We have recently reported that exaggerated oxidative stress in the renal medulla due to superoxide dismutase inhibition resulted in a reduction of renal medullary blood flow and sustained hypertension. The present study tested the hypothesis that selective scavenging of O2-in the renal medulla would prevent hypertension associated with this exaggerated oxidative stress. An indwelling, aortic catheter was implanted in nonnephrectomized Sprague-Dawley rats for daily measurement of arterial blood pressure, and a renal medullary interstitial catheter was implanted for continuous delivery of the superoxide dismutase inhibitor diethyldithiocarbamic acid (DETC, 7.5 mg · kg-1 · d-1) and a chemical superoxide dismutase mimetic, 4-hydroxytetramethyl piperidine-1-oxyl (TEMPOL, 10 mg · kg-1 · d-1). Renal medullary interstitial infusion of TEMPOL completely blocked DETC-induced accumulation of O2·-1 in the renal medulla, as measured by the conversion rate of dihydroethidium to ethidium in the dialysate and by urinary excretion of 8-isoprostanes. However, TEMPOL infusion failed to prevent DETC-induced hypertension, unless catalase (5 mg · kg-1 · d-1) was coinfused, Direct infusion of H2O2 into the renal medulla resulted in increases of mean arterial pressure from 115±2.5 to 131±2.1 mm Hg, which was similar to that observed in rats receiving the medullary infusion of both TEMPOL and DETC. The results indicate that sufficient catalase activity in the renal medulla is a prerequisite for the antihypertensive action of TEMPOL and that accumulated H2O2 in the renal medulla associated with exaggerated oxidative stress might have a hypertensive consequence.

Original languageEnglish (US)
Pages (from-to)25-30
Number of pages6
JournalHypertension
Volume42
Issue number1
DOIs
StatePublished - Jul 1 2003
Externally publishedYes

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Keywords

  • Antioxidants
  • Blood pressure
  • Oxidative stress
  • Renal disease
  • Sodium

ASJC Scopus subject areas

  • Internal Medicine

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