Telmisartan, an
angiotensin II type 1 receptor blocker, reportedly exhibits a partial
peroxisome proliferator-activated receptor (
PPAR)-γ agonistic action. To test whether
telmisartan ameliorates
vascular injury in the
chronic kidney disease model rat through the
PPAR-γ pathway,
telmisartan (5 mg/kg per day, orally),
losartan (5 mg/kg per day, orally) or
telmisartan plus
PPAR-γ antagonist,
GW9662 (1 mg/kg/day, i.p.), was administered for 14 days to subtotal nephrectomized rats (Nx). There was no significant difference in systolic blood pressure or fasting
blood glucose values among all groups. Subtotal
nephrectomy significantly aggravated the levels of urinary
protein excretion, blood
urea nitrogen and plasma
malondialdehyde concentration, which were attenuated by
telmisartan or
losartan treatment. Vasodilation in response to
acetylcholine in the aortic ring was impaired in the Nx, and improved by treatment with
telmisartan. Immunohistochemical analysis revealed that the infiltration of adventitial areas by macrophages and expression of
osteopontin and
vascular cell adhesion molecule-1 were enhanced in the Nx aorta and the overexpression was suppressed by
telmisartan. The increased
NADPH oxidase-derived
superoxide production in the aorta from the Nx rat was suppressed by
telmisartan. Cotreatment with
GW9662 partly blunted the normalization of vascular dysfunction and
inflammation. While
losartan also attenuated these vascular changes in the Nx rats, the extent of the attenuation was significantly greater in the
telmisartan-treated group than in the
losartan-treated group. These results suggest that, in addition to a class effect of
angiotensin II type 1 receptor blockers,
telmisartan exerted vasoprotective effects through its
PPAR-γ agonistic property in rats with
renal failure.