Effects of candesartan cilexetil on oxidative state and renal function in 5/6 nephrectomized rats

Sugimoto, Koichi; Tsuruoka, Shuichi; Matsushita, Kei; Fujimura, Akio

doi:10.1038/sj.jhh.1000743

Cited by 16 publications

(18 citation statements)

References 25 publications

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“…In our study, enalapril (5 mg/kg per day) and vehicle were orally administered once daily by gastric gavage for 16 weeks after 5/6 nephrectomy [3]. Our results showed that lipid peroxides assessed by malondialdehyde content in the homogenate from the renal cortex significantly increased in the nephrectomized rats.…”

mentioning

confidence: 61%

Enalapril on Oxidative Stress in5/6 Nephrectomized Rats

Sugimoto¹,

Tsuruoka²,

Matsushita³

et al. 1999

Nephron

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mentioning

confidence: 61%

Enalapril on Oxidative Stress in5/6 Nephrectomized Rats

Sugimoto¹,

Tsuruoka²,

Matsushita³

et al. 1999

Nephron

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“…The other half (n = 6/group) were provided with plain drinking water for 7 days. The dose of CAN was similar to oral doses used by other investigators [9–11]. …”

Section: Methodsmentioning

confidence: 85%

Candesartan Differentially Regulates Epithelial Sodium Channel in Cortex Versus Medulla of Streptozotocin-Induced Diabetic Rats

Klein¹,

Rash²,

Sands³

et al. 2009

JEBP

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Diabetes is associated with an activated renal renin-angiotensin-aldosterone system (RAAS) and it was shown that streptozotocin (STZ)-induced diabetic rats had increased whole kidney protein levels of the epithelial sodium channel subunits (α-, β-and γ-ENaC). However, the role of the RAAS on the regional, i.e., cortical versus medullary, regulation of ENaC is unclear. Male Sprague-Dawley rats were injected with STZ (intravenous, 65 mg/kg·bw, n=12/group). After 14 days, half of them received drinking water with candesartan (2 mg/kg·bw/day), an angiotensin-II type-1 receptor (AT1R) antagonist, for one week. In the medulla, i.e., inner stripe of the outer medulla (ISOM), base and/or tip of the inner medulla, immunoblotting revealed increased protein abundances of α1 Na-KATPase and ENaC subunits with diabetes (200-600% of controls), which were not reversed by candesartan. In fact, candesartan increased all ENaC subunits and α1 Na-K-ATPase in the ISOM and/or base in control rats. In contrast, in the cortex, diabetes did not increase these proteins. However, candesartan reduced cortical β-and γ-ENaC regardless of diabetic state. In summary, diabetesinduced increases in ENaC were seen preferentially in the medulla. These changes appeared to be due to a mechanism clearly distinct from AT1R activation, because they were not abolished by candesartan. In fact, candesartan treatment tended to increase some of these medullary proteins, perhaps in compensation for increased NaCl load. In contrast, cortical β-and γ-ENaC were reduced by candesartan regardless of diabetic state suggesting their regulation by AT1R at this site; however this did not appear to be a site of diabetes-induced ENaC up-regulation.

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“…Rats were housed singly in microfilter top, plastic cages with a normal 12:12-h light-dark cycle, according to protocols approved by the Georgetown Animal Care and Use Committee. After 1 wk of baseline BP recording (at ϳ9 wk of age), 8 rats from each body type were randomly assigned to either ground control diet (Purina 5001 Rodent Chow, Purina Mills, St. Louis, MO) solidified in agar with 70% water, or the same base diet with 23.5 mg ground CAN cilexetil (Atacand, AstraZeneca Pharmaceuticals, Wilmington, DE) incorporated per kilogram diet (wet weight) to provide a dose of CAN in the range of 3-5 mg ⅐ kg body wt Ϫ1 ⅐ day Ϫ1 , similar to oral doses used by other investigators (26,34,36). Rats were weighed weekly and fed diets and received water ad libitum for 14 wk.…”

Section: Methodsmentioning

confidence: 96%

Chronic candesartan alters expression and activity of NKCC2, NCC, and ENaC in the obese Zucker rat

Halagappa¹,

Tiwari²,

Riazi³

et al. 2008

American Journal of Physiology-Renal Physiology

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The obese Zucker rat reportedly has increased activity of the intrarenal renin-angiotensin-aldosterone system, which conceptually could contribute to elevated salt sensitivity and blood pressure (BP). Our aim was to determine whether there was increased angiotensin II type 1 receptor (AT(1)R)-mediated upregulation of expression or activity of the bumetanide-sensitive Na-K-2Cl cotransporter, the thiazide-sensitive Na-Cl cotransporter (NCC), and/or the epithelial sodium channel (ENaC) in obese vs. lean Zucker rats. Male obese and lean Zucker rats (10-wk old) were fed either 1) control chow (1% NaCl) or 2) chow with candesartan (CAN), an AT(1)R antagonist (25 mg/kg.diet) for 14 wk (n = 8/treatment/body type). BP measured by radiotelemetry, was markedly reduced by CAN ( approximately 20-25 mmHg) in both lean and obese rats with no body-type differences. Obese rats had significantly greater net natriuretic response to single injections of hydrochlorothiazide and benzamil, suggesting increased activity of NCC and ENaC, respectively; however, only the response to benzamil was reduced by CAN. CAN led to a significant reduction in whole kidney levels of NCC and gamma-ENaC (70-kDa band) in both lean and obese rats. However, it significantly increased alpha-ENaC and Na-K-2Cl cotransporter levels, and these increases were greater in obese rats. These studies suggest that relatively increased ENaC, but not NCC activity, in obese rats is due to enhanced AT(1)R activity. CAN attenuated the reduction of several renal transporters in the obese rat kidney. Finally, differences in intrarenal AT(1)R activity do not seem directly responsible for BP differences between lean and obese rats.

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Effects of candesartan cilexetil on oxidative state and renal function in 5/6 nephrectomized rats

Cited by 16 publications

References 25 publications

Enalapril on Oxidative Stress in5/6 Nephrectomized Rats

Enalapril on Oxidative Stress in5/6 Nephrectomized Rats

Candesartan Differentially Regulates Epithelial Sodium Channel in Cortex Versus Medulla of Streptozotocin-Induced Diabetic Rats

Chronic candesartan alters expression and activity of NKCC2, NCC, and ENaC in the obese Zucker rat

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