Open Access
Renoprotective effects of telmisartan in the 5/6 nephrectomised rats
Author(s) -
Ichiro Tsunenari,
Tsuyoshi Ohmura,
Randolph Seidler,
Motohiko Chachin,
Toshihiro Hayashi,
Ayako Konomi,
Takehisa Matsumaru,
Toshiyuki Sumida,
Naoyuki Hayashi,
Yoshiharu Horie
Publication year - 2007
Publication title -
jraas. journal of the renin-angiotensin-aldosterone system/journal of the renin-angiotensin-aldosterone system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.457
H-Index - 46
eISSN - 1752-8976
pISSN - 1470-3203
DOI - 10.3317/jraas.2007.017
Subject(s) - telmisartan , glomerulosclerosis , medicine , urology , nephropathy , enalapril , kidney , immunohistochemistry , endocrinology , proteinuria , angiotensin converting enzyme , blood pressure , diabetes mellitus
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-β1) 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-β1 reactivity in the glomerular tissue tended to decrease in the telmisartan group when compared to the vehicle group. Thus, the progressive 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. pharmacological properties of telmisartan, clinical studies have been conducted to evaluate the clinical effectiveness and safety of telmisartan on diabetic nephropathy in patients with type 2 diabetes. It has been reported that telmisartan arrested progressive renal dysfunction in hypertensive patients with early-stage diabetic nephropathy. Makino et al. 8 reported the effectiveness of this drug therapy in suppressing the progression of nephropathy in type 2 diabetic patients with or without hypertension, without serious safety concerns. Remuzzi and Remuzzi 9 reviewed the potential protective effects of telmisartan on renal function deterioration and suggested that telmisartan may effectively ameliorate renal dysfunction in patients affected by the metabolic syndrome. In addition, telmisartan also showed renoprotective effects in some animal models: spontaneously hypertensive rats (SHR), 10 as well as the hypertensive diabetic model that combines SHR with streptozotocininduced diabetes. 11 Ohmura et al. 12 investigated the mechanism of the renoprotective effect of telmisartan using obese Zucker diabetic rats. Ciclosporin A-induced nephropathy in pigs was attenuated by telmisartan without any reduction of blood pressure (BP). 13 This animal data suggested that the suppressive effect on the progression of nephropathy might be due to both haemodynamic and non-haemodynamic action(s) of the drug.