title: Effect of nitric oxide pathway regulation on water/sodium balance and renal function in a rodent model of acute liver and renal failure.
abstract: BACKGROUND
  The pathomechanism of acute hepatorenal syndrome (HRS), a particular form of acute renal failure that occurs in the course of acute liver injury, is still poorly understood. The aim of our study was to estimate the influence of the activation and inhibition of the nitric oxide pathway on the water/sodium balance and development of acute renal failure in the course of HRS.
  
  
  METHODS
  We used male Sprague-Dawley rats in the acute galactosamine (Ga1N) model of HRS. The nitric oxide synthase (NOS) inhibitors L-NAME and L-arginine were administered intraperitoneally before and after liver damage.
  
  
  RESULTS
  HRS developed in all tested groups. L-NAME increased osmotic clearance and urine volume more effectively before liver injury. Furthermore, administration of L-NAME increased creatinine clearance both before and after Ga1N injection. A double dose of L-NAME did not yield further improvement before Ga1N injection, but improved creatinine clearance after Ga1N intoxication. Injection of L-arginine increased sodium excretion and urine volume, but only after liver injury. Moreover, L-arginine injected after Ga1N caused significant improvement of the creatinine clearance in a dose-dependent manner.
  
  
  CONCLUSIONS
  Our study shows that inhibition of the nitric oxide pathway improves parameters of water and sodium balance and prevents development of acute renal failure in the course of acute liver injury and liver failure. Activation of the nitric oxide system also has a favorable influence on water/sodium balance and renal failure, but only after liver injury.
authors.affiliation: Department of Internal Diseases, Nephrology and Dialysis, Military Institute of Medicine, Warsaw, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Saracyn
authors.affiliation: Department of Urology, Military Institute of Medicine, Warsaw, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Ząbkowski
authors.affiliation: Department of Regenerative Medicine, Military Institute of Hygiene and Epidemiology, Warsaw, Poland.
authors.forename: Robert
authors.initials: R
authors.lastname: Zdanowski
authors.affiliation: Department of Pharmacology and Toxicology, Military Institute of Hygiene and Epidemiology, Warsaw, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Brytan
authors.affiliation: Department of Pathology, Military Institute of Medicine, Warsaw, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Patera
authors.affiliation: Department of Internal Diseases, Nephrology and Dialysis, Military Institute of Medicine, Warsaw, Poland.
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Nowak
authors.affiliation: Department of Internal Diseases, Nephrology and Dialysis, Military Institute of Medicine, Warsaw, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Kade
authors.affiliation: Department of Internal Diseases, Nephrology and Dialysis, Military Institute of Medicine, Warsaw, Poland.
authors.forename: Zofia
authors.initials: Z
authors.lastname: Wańkowicz
mesh_terms: D058186:Acute Kidney Injury / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology*; D000818:Animals; D003404:Creatinine / Q000378:metabolism; D004195:Disease Models, Animal; D007668:Kidney / Q000473:pathology / Q000503:physiopathology*; D007677:Kidney Function Tests; D008099:Liver / Q000473:pathology; D017114:Liver Failure, Acute / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009569:Nitric Oxide / Q000378:metabolism*; D009994:Osmolar Concentration; D017207:Rats, Sprague-Dawley; D014882:Water-Electrolyte Balance
chemical_list: D009569:Nitric Oxide; D003404:Creatinine; D019331:NG-Nitroarginine Methyl Ester