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on June 2, 2003

A more recent version of this article appeared on July 1, 2003

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Submitted on January 24, 2003
Revised on February 12, 2003

Increased Renal Medullary H₂O₂ Leads to Hypertension

Ayako Makino; Meredith M. Skelton; Ai-Ping Zou; and Allen W. Cowley Jr^*

From the Department of Physiology, Medical College of Wisconsin, Milwaukee.

^* To whom correspondence should be addressed. E-mail: cowley{at}mcw.edu.

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^.- 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.

Key words: oxidative stress • blood pressure • antioxidants • renal disease • sodium

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