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, Allen W. Cowley

Research output: Contribution to journalArticle

59 Citations (Scopus)

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), 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 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 mTAL. The O2 diffused to adjoining pericytes in tissue strips only in SS/Mcwi rats but not in control SS-13 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.

Original languageEnglish (US)
Pages (from-to)1336-1341
Number of pages6
JournalHypertension
Volume49
Issue number6
DOIs
StatePublished - Jun 1 2007

Fingerprint

Inbred Dahl Rats
Superoxides
Blood Vessels
Nitric Oxide
Pericytes
Extremities
Kidney
Rectum
Angiotensin II
Fluorescence Microscopy
Biological Availability
Free Radicals
Reactive Oxygen Species
Fibrosis
Salts
Epithelial Cells

Keywords

  • Cross-talk
  • Dahl rat
  • NO
  • Renal medulla
  • Superoxide

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Enhanced superoxide production in renal outer medulla of dahl salt-sensitive rats reduces nitric oxide tubular-vascular cross-talk. / Mori, Takefumi; O'Connor, Paul M.; Abe, Michiaki; Cowley, Allen W.

In: Hypertension, Vol. 49, No. 6, 01.06.2007, p. 1336-1341.

Research output: Contribution to journalArticle

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AB - 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), 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 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 mTAL. The O2 diffused to adjoining pericytes in tissue strips only in SS/Mcwi rats but not in control SS-13 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.

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