TY - JOUR

T1 - Chronic nitric oxide synthase inhibition exacerbates renal dysfunction in cirrhotic rats

AU - Graebe, Martin

AU - Brond, Lone

AU - Christensen, Sten

AU - Nielsen, Soren

AU - Olsen, Niels Vidiendal

AU - Jonassen, Thomas E N

PY - 2004/2

Y1 - 2004/2

N2 - 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.

AB - 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.

KW - Aldosterone

KW - Animals

KW - Blotting, Western

KW - Common Bile Duct

KW - Enzyme Inhibitors

KW - Female

KW - Glomerular Filtration Rate

KW - Kidney Cortex

KW - Kidney Diseases

KW - Kidney Tubules, Proximal

KW - Ligation

KW - Lithium

KW - Liver Cirrhosis

KW - NG-Nitroarginine Methyl Ester

KW - Nitric Oxide Synthase

KW - Rats

KW - Rats, Wistar

KW - Renal Circulation

KW - Sodium

KW - Sodium-Hydrogen Antiporter

KW - Sodium-Potassium-Exchanging ATPase

KW - Specific Pathogen-Free Organisms

U2 - 10.1152/ajprenal.00089.2003

DO - 10.1152/ajprenal.00089.2003

M3 - Journal article

C2 - 14583432

VL - 286

SP - F288-97

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

IS - 2

ER -