Renoprotective effects of telmisartan on renal injury in obese Zucker rats.
The purpose of the present study was to investigate the renoprotective effect of telmisartan, an angiotensin II receptor antagonist, on the early stages of diabetic nephropathy in obese Zucker rats, which is a type 2-related diabetes mellitus model. Telmisartan 1, 3 or 10 mg/kg/day was orally administered to 7-week-old rats that demonstrated glucose tolerance without albuminuria or proteinuria, for 24 consecutive weeks (Experiment A). In another experiment (Experiment B), oral administration of telmisartan 10 mg/kg/day was initiated at the age of 16 weeks after the rats demonstrated marked proteinuria, and continued for 24 weeks. Telmisartan inhibited the increase in proteinuria and albuminuria in a dose-dependent manner, and the inhibition for all telmisartan groups was statistically significant by the completion of administration (Experiment A). Telmisartan also displayed similar inhibitory effects on proteinuria and albuminuria in Experiment B. Histologically, telmisartan [3 and 10 mg/kg/day] was associated with a significant decrease in the progression of glomerulosclerosis, and significantly improved interstitial cell infiltration, interstitial fibrosis and dilation and atrophy of renal tubules. Furthermore, telmisartan treatment was associated with a tendency towards normalized plasma lipids (total cholesterol and triglyceride). Our results suggest that telmisartan has a definite renoprotective effect against renal injury in type II diabetic nephropathy.
Ohmura
T
T
Project Coordination Group, Kawanishi Pharma Research Institute, Nippon Boehringer Ingelheim Co, Ltd, Yato, 3-10-1 Kawanishi, Hyogo, Japan. ohmura@kaw.boehringer-ingelheim.com
Tsunenari
I
I
Seidler
R
R
Chachin
M
M
Hayashi
T
T
Konomi
A
A
Matsumaru
T
T
Sumida
T
T
Hayashi
N
N
Horie
Y
Y
D000419:Albuminuria / Q000188:drug therapy; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage*; D001565:Benzoates / Q000008:administration & dosage*; D002784:Cholesterol / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control*; D006801:Humans; D007668:Kidney / Q000187:drug effects; D008297:Male; D011507:Proteinuria / Q000188:drug therapy; D051381:Rats; D011924:Rats, Zucker; D000077333:Telmisartan; D014280:Triglycerides / Q000378:metabolism; D014556:Urine / Q000737:chemistry
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D014280:Triglycerides; D002784:Cholesterol; D000077333:Telmisartan