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.