Effect of Nitric Oxide Pathway Regulation on Water/Sodium Balance and Renal Function in a Rodent Model of Acute Liver and Renal Failure
Marek Saracyn, Tomasz Ząbkowski, Robert Zdanowski, Marek Brytan, Janusz Patera, Zbigniew Nowak, Grzegorz Kade, Zofia Wańkowicz
Department of Internal Diseases, Nephrology and Dialysis, Military Institute of Medicine, Warsaw, Poland
Med Sci Monit 2014; 20:1735-1744
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.
Material and 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.
Keywords: Creatinine - metabolism, Animals, Acute Kidney Injury - physiopathology, Disease Models, Animal, Kidney - physiopathology, Kidney Function Tests, Liver - pathology, Liver Failure, Acute - physiopathology, NG-Nitroarginine Methyl Ester - administration & dosage, Nitric Oxide - metabolism, Osmolar Concentration, Rats, Sprague-Dawley, Water-Electrolyte Balance