NDT Advance Access originally published online on September 2, 2005
Nephrology Dialysis Transplantation 2005 20(12):2670-2680; doi:10.1093/ndt/gfi045
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Telmisartan inhibits both oxidative stress and renal fibrosis after unilateral ureteral obstruction in acatalasemic mice
1 Department of Medicine and Clinical Science, 2 Department of Public Health and 3 Department of Biochemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan
Correspondence and offprint requests to: Dr Hitoshi Sugiyama, Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. Email: hitoshis{at}md.okayama-u.ac.jp
Background. Reactive oxygen species are involved in many of the angiotensin II signalling pathways. We have thus investigated whether the angiotensin II type 1 (AT1) receptor antagonist, telmisartan, can inhibit the accelerated renal fibrosis and excess oxidative stress, which occurs after unilateral ureteral obstruction (UUO) in acatalasemic mice.
Methods. The effect of daily intraperitoneal injection of telmisartan (0.1–0.3 mg/kg body weight) on the renal tubulointerstitial injury induced by UUO has been studied in homozygous acatalasemic mutant mice (C3H/AnLCsbCsb) and wild-type mice (C3H/AnLCsaCsa). We evaluated the systemic blood pressure of the mice on the seventh day. In addition, the tubulointerstitial expression of collagens type I and type IV, the p22-, p47- and p67-phox subunits of NADPH oxidase, 4-hydroxy-2-nonenal, and 4-hydroxy-2-hexenal lipid peroxidation products were assessed by immunohistochemistry. The level of apoptosis was determined by terminal deoxynucleotidyl transferase nick end-labelling analysis, while the mRNA level of the p22-, p47- and p67-phox subunits was quantified by real-time PCR. The renal content of each of the antioxidant enzymes catalase, glutathione peroxidase and superoxide dismutase was determined by specific assay.
Results. Obstructed kidneys from acatalasemic mice exhibited increased tubulointerstitial deposition in dilated tubules of collagens type I and IV, lipid peroxidation products, and the p22/p47/p67-phox subunits of NADPH oxidase. The level of the p22/p47/p67-phox subunit mRNA, and of apoptosis in tubular epithelial cells, was also increased compared with those from wild-type kidneys. Treatment with telmisartan attenuated all of the changes and prevented renal fibrosis in a dose-dependent manner; despite the low dose (0.1 mg/kg). The treatment did not lower the systemic blood pressure. The catalase activity remained low in acatalasemic obstructed kidneys without compensatory upregulation of glutathione peroxidase or superoxide dismutase activity; the level of neither anti-oxidant enzymes in obstructed kidneys was affected by telmisartan.
Conclusions. The AT1 receptor antagonist telmisartan ameliorated renal fibrosis after UUO by inhibition of oxidative stress, even under acatalasemic conditions.
Keywords: acatalasemia; angiotensin II receptor antagonist; apoptosis; catalase; NADPH oxidase
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Carlstrom, R. D. Brown, J. Sallstrom, E. Larsson, M. Zilmer, S. Zabihi, U. J. Eriksson, and A. E. G. Persson SOD1 deficiency causes salt sensitivity and aggravates hypertension in hydronephrosis Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2009; 297(1): R82 - R92. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Satoh, S. Fujimoto, S. Arakawa, T. Yada, T. Namikoshi, Y. Haruna, H. Horike, T. Sasaki, and N. Kashihara Angiotensin II type 1 receptor blocker ameliorates uncoupled endothelial nitric oxide synthase in rats with experimental diabetic nephropathy Nephrol. Dial. Transplant., December 1, 2008; 23(12): 3806 - 3813. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Quinlan, N. G. Docherty, R. W. G. Watson, and J. M. Fitzpatrick Exploring mechanisms involved in renal tubular sensing of mechanical stretch following ureteric obstruction Am J Physiol Renal Physiol, July 1, 2008; 295(1): F1 - F11. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Carlstrom, E. Y. Lai, A. Steege, M. Sendeski, Z. Ma, S. Zabihi, U. J. Eriksson, A. Patzak, and A. E. G. Persson Nitric Oxide Deficiency and Increased Adenosine Response of Afferent Arterioles in Hydronephrotic Mice With Hypertension Hypertension, May 1, 2008; 51(5): 1386 - 1392. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Carlstrom, R. D. Brown, J. Edlund, J. Sallstrom, E. Larsson, T. Teerlink, F. Palm, N. Wahlin, and A. E. G. Persson Role of nitric oxide deficiency in the development of hypertension in hydronephrotic animals Am J Physiol Renal Physiol, February 1, 2008; 294(2): F362 - F370. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Remuzzi and G. Remuzzi Review: Potential protective effects of telmisartan on renal function deterioration Journal of Renin-Angiotensin-Aldosterone System, December 1, 2006; 7(4): 185 - 191. [Abstract] [PDF]
|
|