Renoprotective effects of telmisartan on renal injury in obese Zucker rats

Ohmura, Tsuyoshi; Tsunenari, Ichiro; Seidler, Randolph; Chachin, Motohiko; Hayashi, Taihei; Konomi, Ayako; Matsumaru, Takehisa; Sumida, Toshiyuki; Hayashi, Naoyuki; Horie, Yoshiharu

doi:10.1007/s00592-007-0016-5

Cited by 16 publications

(19 citation statements)

References 35 publications

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“…22 In addition, the progression assessed by biochemical parameters in this model was more rapid than that in the obese Zucker rats, a model of type 2 diabetes. 12 The histopathological lesions in this model were also more severe than those in the obese Zucker rats. 12 Thus, the 5/6 Nx in rats induced characteristic signs of progressive diabetic nephropathy.…”

Section: Figurementioning

confidence: 92%

“…12 The histopathological lesions in this model were also more severe than those in the obese Zucker rats. 12 Thus, the 5/6 Nx in rats induced characteristic signs of progressive diabetic nephropathy.…”

Section: Figurementioning

confidence: 92%

“…The effectiveness of telmisartan in suppressing the progression of renal injury in early-stage nephropathy was previously reported not only in the rat model of diabetes 12 but also in patients with type 2 diabetes. 7,8 In addition, telmisartan attenuated ciclosporin A-induced nephropathy in pigs without any antihypertensive effects.…”

mentioning

confidence: 96%

“…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).…”

Section: Introductionmentioning

confidence: 99%

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Renoprotective effects of telmisartan in the 5/6 nephrectomised rats

Tsunenari¹,

Ohmura

Seidler

et al. 2007

J Renin Angiotensin Aldosterone Syst

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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 Remuzzi9 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.

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Section: Figurementioning

confidence: 92%

Section: Figurementioning

confidence: 92%

mentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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Renoprotective effects of telmisartan in the 5/6 nephrectomised rats

Tsunenari¹,

Ohmura

Seidler

et al. 2007

J Renin Angiotensin Aldosterone Syst

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“…On the contrary, another line of evidence suggests that long-term telmisartan treatment can improve insulin resistance and metabolic parameters and decrease blood pressure, all of which are beneficial to the kidney. 20,31 Therefore, it is difficult to precisely assess how much the indirect renoprotective effect of telmisartan contributes to amelioration of kidney damage in MetS rats. Future studies should address this issue.…”

Section: Discussionmentioning

confidence: 99%

Telmisartan Ameliorates Nephropathy in Metabolic Syndrome by Reducing Leptin Release From Perirenal Adipose Tissue

Liu

et al. 2016

Hypertension

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Abstract-Metabolic syndrome (MetS) is associated with nephropathy. Along with common risk factors such as hypertension and hyperglycemia, adipocytokines released from perirenal adipose tissue (PRAT) are implicated in the pathogenesis of MetS nephropathy. The study was designed to elucidate the adverse effects of PRAT-derived leptin on nephropathy and to determine whether the angiotensin II type 1 receptor antagonist telmisartan exerts a renoprotective effect by decreasing the PRAT-derived leptin level in the high-fat diet-induced MetS rat. In MetS rats, PRAT-derived leptin expression increased concomitant with dysfunction of adipogenesis, and the activities of the angiotensin II-angiotensin II type 1 receptor and the angiotensin-converting enzyme 2-angiotensin (1-7)-Mas receptor axes were imbalanced in PRAT. PRAT-derived leptin from MetS rats promoted proliferation of rat glomerular endothelial cells (GERs) by activating the p38 MAPK (mitogenactivated protein kinase) pathway, thereby contributing to the development of nephropathy. Long-term telmisartan treatment improved metabolic parameters and renal function, decreased the amount of PRAT, promoted adipogenesis, increased the expression of angiotensin-converting enzyme 2, restored balanced activities of the angiotensin II-AT1R and angiotensin-converting enzyme 2-angiotensin (1-7)-Mas axes, and exerted an indirect renoprotective effect on MetS rats by decreasing PRAT-derived leptin release. Our results demonstrate a novel link between nephropathy and PRAT in MetS and show that telmisartan confers an underlying protective effect on visceral adipose tissue and the kidney, suggesting that it has potential as a therapeutic agent for the treatment of MetS-associated nephropathy. (Hypertension. 2016;68:478-490.

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