Human
autosomal recessive polycystic kidney disease (
ARPKD) produces kidneys which are massively enlarged due to multiple
cysts,
hypertension, and
congenital hepatic fibrosis characterized by dilated bile ducts and
portal hypertension. The PCK rat is an orthologous model of human
ARPKD with numerous fluid-filled
cysts caused by stimulated cellular proliferation in the renal tubules and hepatic bile duct epithelia, with interstitial
fibrosis developed in the liver. We previously reported that a
peroxisome proliferator activated receptor (
PPAR)-γ full agonist ameliorated kidney and
liver disease in PCK rats.
Telmisartan is an
angiotensin receptor blocker (ARB) used widely as an
antihypertensive drug and shows partial
PPAR-γ agonist activity. It also has nephroprotective activity in diabetes and renal injury and prevents the effects of
drug-induced hepatotoxicity and hepatic
fibrosis. In the present study, we determined whether
telmisartan ameliorates progression of
polycystic kidney and fibrocystic
liver disease in PCK rats. Five male and 5 female PCK and normal control (+/+) rats were orally administered 3 mg/kg
telmisartan or vehicle every day from 4 to 20 weeks of age. Treatment with
telmisartan decreased blood pressure in both PCK and +/+ rats. Blood levels of
aspartate amino
transferase,
alanine amino
transferase and
urea nitrogen were unaffected by
telmisartan treatment. There was no effect on
kidney disease progression, but liver weight relative to
body weight, liver cystic area, hepatic
fibrosis index, expression levels of Ki67 and TGF-β, and the number of Ki67- and TGF-β-positive interstitial cells in the liver were significantly decreased in
telmisartan-treated PCK rats. Therefore,
telmisartan ameliorates
congenital hepatic fibrosis in
ARPKD, possibly through the inhibition of signaling cascades responsible for cellular proliferation and interstitial
fibrosis in PCK rats. The present results support the potential
therapeutic use of ARBs for the treatment of fibrocystic
liver disease in
ARPKD patients.