Inducible nitric oxide synthase and glomerular hemodynamics in rats with liver cirrhosis

This study was designed to test the hypothesis that glomerular de novo expr ession of inducible nitric oxide synthase (iNOS) contributes to renal hemod ynamic abnormalities in liver cirrhosis developed 3 wk after common bile du ct ligature (CBDL). De novo expression of iNOS mRNA was detected by RT-PCR in RNA extracts from isolated CBDL rat glomeruli whereas no iNOS mRNA was f ound in control rat glomerular RNA. Immunohistochemical staining for iNOS w as negative in control animals whereas, in CBDL rats, positive iNOS stainin g was detected in an apparently mesangial pattern in all glomeruli. Western blots of protein extracts from isolated glomeruli of CBDL rats, but not co ntrol animals, showed a prominent iNOS band of 130 kDa. Mean arterial press ure (MAP), renal plasma flow (RPF; p-aminohippurate clearance), and glomeru lar filtration rate (GFR; inulin clearance) were unaltered in CBDL rats, bu t the application of 4 mg/kg L-N(6)-(1-iminoethyl) lysine, a specific inhib itor of iNOS, reduced GFR and RPF significantly in CBDL rats, whereas contr ol animals were not affected. Similar results were obtained with lipopolysa ccharide (LPS) pretreated animals, which were studied as a positive control for iNOS expression and as a model for recent iNOS induction. We conclude that de novo expression of iNOS occurs in glomeruli of rats with liver cirr hosis and that nitric oxide, generated by iNOS, contributes to the maintena nce of glomerular filtration in the early state of this disease.