Chronic nitric oxide synthase inhibition exacerbates renal dysfunction in cirrhotic rats

Martin Graebe, Lone Brond, Sten Christensen, Soren Nielsen, Niels Vidiendal Olsen, Thomas E N Jonassen

21 Citations (Scopus)

Abstract

The present study investigated sodium balance and renal tubular function in cirrhotic rats with chronic blockade of the nitric oxide (NO) system. Rats were treated with the nonselective NO synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME) starting on the day of common bile duct ligation (CBL). Three weeks of daily sodium balance studies showed that CBL rats developed sodium retention compared with sham-operated rats and that l-NAME treatment dose dependently deteriorated cumulative sodium balance by reducing urinary sodium excretion. Five weeks after CBL, renal clearance studies were performed, followed by Western blotting of the electroneutral type 3 sodium/proton exchanger (NHE3) and the Na-K-ATPase present in proximal tubules. Untreated CBL rats showed a decreased proximal reabsorption with a concomitant reduction of NHE3 and Na-K-ATPase levels, indicating that tubular segments distal to the proximal tubules were responsible for the increased sodium reabsorption. l-NAME-treated CBL rats showed an increased proximal reabsorption measured by the lithium clearance method and showed a marked increase in NHE3 and Na-K-ATPase protein levels. Our results show that chronic l-NAME treatment exacerbates the sodium retention found in CBL rats by a significant increase in proximal tubular reabsorption.
Original languageEnglish
JournalAmerican Journal of Physiology: Renal Physiology
Volume286
Issue number2
Pages (from-to)F288-97
ISSN1931-857X
DOIs
Publication statusPublished - Feb 2004

Keywords

  • Aldosterone
  • Animals
  • Blotting, Western
  • Common Bile Duct
  • Enzyme Inhibitors
  • Female
  • Glomerular Filtration Rate
  • Kidney Cortex
  • Kidney Diseases
  • Kidney Tubules, Proximal
  • Ligation
  • Lithium
  • Liver Cirrhosis
  • NG-Nitroarginine Methyl Ester
  • Nitric Oxide Synthase
  • Rats
  • Rats, Wistar
  • Renal Circulation
  • Sodium
  • Sodium-Hydrogen Antiporter
  • Sodium-Potassium-Exchanging ATPase
  • Specific Pathogen-Free Organisms

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