Renoprotective effects of telmisartan in the 5/6 nephrectomised rats.
The purpose of this study was to investigate the renoprotective effect of telmisartan on the advanced stages of nephropathy in rats with 5/6 nephrectomy (5/6 Nx). Telmisartan was orally administered for 12 weeks to rats that previously underwent 5/6 Nx or sham operations. After completion of the administration period, the degree of renal injury was examined histopathologically using indices of glomerulosclerosis and lesions of the renal tubule and interstitium. An immunohistochemical staining for transforming growth factor-beta (TGF-beta1) was also performed. The suppression of urinary protein was statistically significant in surviving animals dosed with telmisartan. The enalapril group's urinary protein was also significantly suppressed for these same parameters in surviving animals. Histopathologically, telmisartan significantly decreased the progression of glomerulosclerosis and the interstitial cell infiltration at all doses tested. As assessed by immunohistochemical staining the TGF-beta1 reactivity in the glomerular tissue tended to decrease in the telmisartan group when compared to the vehicle group. Thus, telmisartan ameliorates the progressive nephropathy in the remaining kidney after 5/6 Nx by non-haemodynamic as well as antihypertensive actions of the drug.
Tsunenari
Ichiro
I
Pharmacokinetics and Non-Clinical Safety Department, Kawanishi Pharma Research Institute, Nippon Boehringer Ingelheim Co., Ltd., 3-10-1 Yato, Kawanishi, Japan. tsunenari@kaw.boehringeringelheim.com
Ohmura
Tsuyoshi
T
Seidler
Randolph
R
Chachin
Motohiko
M
Hayashi
Toshihiro
T
Konomi
Ayako
A
Matsumaru
Takehisa
T
Sumida
Toshiyuki
T
Hayashi
Naoyuki
N
Horie
Yoshiharu
Y
D047228:Angiotensin II Type 1 Receptor Blockers / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D001562:Benzimidazoles / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001565:Benzoates / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D004195:Disease Models, Animal; D004656:Enalapril / Q000627:therapeutic use; D007668:Kidney / Q000473:pathology; D009392:Nephrectomy; D051381:Rats; D000077333:Telmisartan
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D004656:Enalapril; D000077333:Telmisartan