M. Ubeda et al., RENIN AND ANGIOTENSINOGEN MESSENGER-RNA EXPRESSION IN THE KIDNEYS OF RATS SUBJECTED TO LONG-TERM BILE-DUCT LIGATION, Hepatology, 19(6), 1994, pp. 1431-1436
Activation of antinatriuretic systems such as the renin-angiotensin sy
stem, is of major importance in the pathogenesis of sodium retention i
n cirrhosis. In this study, we studied the intrarenal renin angiotensi
n system by measuring renin and angiotensinogen mRNA expression in the
kidney of rats subjected to long-term bile duct ligation in a phase b
efore the development of ascites, when sodium retention is already pre
sent. Experiments were performed in sham-operated and bile duct-ligate
d rats 3 wk after surgery. Balance studies showed lower sodium excreti
on and greater sodium retention in the bile duct-ligated rats compared
with the control animals. Plasma renin activity (4.41 +/- 1.01 ng Ang
iotensin I/ml/hr in the bile duct-ligated group vs, 4.20 +/- 0.74 in t
he controls) and plasma renin concentration were not different between
the two groups. However, plasma renin substrate was significantly dec
reased in bile duct-ligated animals. Total kidney renin mRNA was signi
ficantly higher in the bile duct-ligated animals (0.83 +/- 0.14 densit
ometric units vs. 0.44 +/- 0.04 in the controls), as determined on Nor
thern-blot analysis and densitometric quantitation. Angiotensinogen mR
NA expression in the kidneys of bile duct-ligated rats was significant
ly decreased (0.09 +/- 0.01 densitometric units) compared with that of
the controls (0.21 +/- 0.03). These results indicate that sodium-reta
ining, nonascitic bile duct-ligated rats show abnormalities of the int
rarenal renin angiotensin system that precede changes in plasma renin
activity. Our data suggest that the intrarenal renin angiotensin syste
m may participate in the initiation of the renal pathophysiological ab
normalities present in bile duct-ligated rats.