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Telmisartan attenuates peritoneal fibrosis via peroxisome proliferator‐activated receptor‐ γ activation in rats
Author(s) -
Su Xuesong,
Yu Rui,
Yang Xu,
Zhou Guangyu,
Wang Yanqiu,
Li Li,
Li Detian
Publication year - 2015
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12403
Subject(s) - telmisartan , endocrinology , fibrosis , mapk/erk pathway , medicine , peritoneum , receptor , masson's trichrome stain , peritoneal dialysis , peroxisome proliferator activated receptor , chemistry , pharmacology , kinase , pathology , biochemistry , blood pressure
Summary Peritoneal dialysis ( PD ) is an effective treatment for patients with end‐stage renal diseases, but long‐term continuous PD causes peritoneal fibrosis ( PF ). This study aims to evaluate the anti‐fibrotic effect of telmisartan on a rat model of PF and to investigate the underlying mechanisms. Five‐sixths kidney nephrectomy and PD were used to establish the PF rat model. Glucose (2.5%) was used to establish an in vitro model in rat peritoneal mesothelial cells ( PMC ). Haematoxylin–eosin staining was used to examine the structural alterations. Masson's trichrome staining was used to observe the tissue fibrosis in peritoneal membrane of rats. Real‐time polymerase chain reaction was used to measure messenger RNA expressions of profibrotic factors. Western blotting was used to determine protein expressions of profibrotic factors, peroxisome proliferator‐activated receptor‐ γ , and mitogen‐activated protein kinases (MAPK). Results demonstrated that administration of telmisartan dose‐dependently attenuated the thickening of the peritoneal membrane and the fibrosis induced by long‐term PD fluid exposure in rats. In addition, telmisartan treatment inhibited the upregulation of profibrotic factors induced by PD in the peritoneum of rats and by high‐concentration glucose in PMC . Telmisartan was also effective in inhibiting PD and high‐concentration, glucose‐induced phosphorylation of MAPK in the peritoneum and PMC . Furthermore, peroxisome proliferator‐activated receptor‐ γ (PPAR γ ) inhibitor GW 9662 blocked these protective effects of telmisartan in PMC . The results suggest that telmisartan is effective in attenuating PD ‐induced PF , and this effect may be associated with the inhibition of profibrotic factor expression and MAPK phosphorylation via PPAR γ activation.