Strain of experimental animals and modulation of nitric oxide pathway: their influence on development of renal failure in an experimental model of hepatorenal syndrome

Abstract

Introduction: Pathomechanism of HRS is still poorly understood. The aim of our study was: (1) to test whether different strains of rats could develop typical HRS, and (2) to estimate the influence of activation and inhibition of nitric oxide for development of renal failure in course of HRS.

Material and methods: First, we used 16 of Wistar and 16 of Sprague-Dawley rats in galactosamine model of HRS. Next, we used 48 of SDR rats, which received saline, N-nitro-L-arginine or L-arginine before and after liver damage. Twenty four hours urine and blood samples were collected 48 h after saline or Ga1N injection. Biochemical parameters were determined in serum or urine and then creatinine clearance and osmolality clearance were calculated. Liver and kidney tissues were collected for histopathological examination.

Results: Liver failure developed in all tested groups with significant increase of bilirubin (p < 0.001), ALT (p < 0.001) and ammonia (p < 0.001). Nevertheless we did not achieve any evidence of renal failure in Wistar, but we found typical renal failure in Sprague-Dawley group with significant decrease in creatinine clearance (p < 0.0012) and increase in concentration of creatinine and urea (p < 0.001) and (p < 0.001) respectively. Inhibition of NOS prevented development of renal failure with significant improvement of GFR both before (p < 0.0017) and after (p < 0.003) Ga1N injection. Injection of L-arginine after Ga1N injection did not caused significant improvement of GFR.

Conclusions: Our study showed, that genetic factors might be responsible for development of renal failure in course of HRS and nitric oxide play important role in acute model of this syndrome.

Keywords: experimental studies; hepatorenal syndrome; nitric oxide.

Figure 1

Influence of L-NAME injection on creatinine clearance before and after liver injury. Inhibition of NO system before Ga1N intoxication significantly increased GFR. Inhibition of NOS after Ga1N intoxication also resulted in significant improvement of GFR, but to a lesser degree than in the case of treatment before intoxication. Values are means ± SE, significance – p < 0.05

Figure 2

Influence of L-ARG injection on creatinine clearance before and after liver injury. Activation before liver damage did not significantly change level of GFR. However, using a donor for the NO system after Ga1N intoxication brought improvement of glomerular filtration, although not significantly. Values are means ± SE, significance – p < 0.05

Figure 3

Histopathological picture of the liver in SDR. A – Lack of morphological changes in the liver from sham SDR rats (group 4) at 48 h after saline injection. Haematoxilin and eosin staining, light microscope, magnification 10×. B – Massive necrosis of hepatocytes in the liver from tested SDR rats (group 5) at 48 h after galactosamine injection. Haematoxilin and eosin staining, light microscope, magnification 10×

Figure 4

Histopathological picture of the kidney in SDR. A – Lack of morphological changes in the kidney from sham SDR rats (group 4) at 48 h after saline injection. Hematoxilin and eosin staining, light microscope, magnification 10×. B – Lack of morphological changes in the kidney from tested SDR rats (group 5) at 48 h after galactosamine injection. Hematoxilin and eosin staining, light microscope, magnification 10×