Published Online
on April 30, 2007

A more recent version of this article appeared on June 1, 2007

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Submitted on December 8, 2006
Revised on January 4, 2007

Enhanced Superoxide Production in Renal Outer Medulla of Dahl Salt-Sensitive Rats Reduces Nitric Oxide Tubular-Vascular Cross-Talk

Takefumi Mori; Paul M. O’Connor; Michiaki Abe; 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--Studies were conducted to determine whether the diffusion of NO from the renal medullary thick ascending limb (mTAL) to the contractile pericytes of surrounding vasa recta was reduced and, conversely, whether diffusion of oxygen free radicals was enhanced in the salt-sensitive Dahl S rat (SS/Mcwi). Angiotensin II ([Ang II] 1 µmol/L)-stimulated NO and superoxide (O₂^·-) production were imaged by fluorescence microscopy in thin tissue strips from the inner stripe of the outer medulla. In prehypertensive SS/Mcwi rats and a genetically designed salt-resistant control strain (consomic SS-13^BN), Ang II failed to increase either NO or O₂^·- in pericytes of isolated vasa recta. Ang II stimulation resulted in production of NO in epithelial cells of the mTAL that diffused to vasa recta pericytes of SS-13^BN rats but not in SS/Mcwi rats except when tissues were preincubated with the superoxide scavenger TIRON (1 mmol/L). Ang II resulted in a greater increase of O₂^·- in the mTAL of SS/Mcwi compared with SS.13^BN mTAL. The O₂^·- diffused to adjoining pericytes in tissue strips only in SS/Mcwi rats but not in control SS-13^BN rats. Diffusion of Ang II-stimulated O₂^·- from mTAL to vasa recta pericytes was absent when tissue strips from SS/Mcwi rats were treated with the NO donor DETA-NONOate (20 µmol/L). We conclude that the SS/Mcwi rat exhibits increased production of O₂^·- in mTAL that diffuses to surrounding vasa recta and attenuates NO cross-talk. Diffusion of O₂^·- from mTAL to surrounding tissue could contribute to reduced bioavailability of NO, reductions of medullary blood flow, and interstitial fibrosis in the outer medulla of SS/Mcwi rats.

Key words: Dahl rat • NO • superoxide • renal medulla • cross-talk

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