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Involvement of vascular endothelial nitric oxide synthase in development of experimental diabetic nephropathy in rats

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Abstract

Endothelial nitric-oxide synthase (eNOS) acts as a common pathogenic pathway in diabetic nephropathy (DN). However, its functional consequences are still not fully understood. Caveolin, a membrane protein, inhibits the eNOS by making caveolin–eNOS complex, and its expression is upregulated during diabetes mellitus (DM). This study was designed to determine the role of caveolin in eNOS-mediated NO synthesis and release in DN. DM in rat was induced by feeding of high-fat diet (HFD) for 2 weeks, followed by single dose of streptozotocin (STZ) (35 mg/kg, ip) further followed by HFD for further 8 weeks. Serum nitrite/nitrate ratio was measured to determine the plasma level of NO. Diabetic rat, after 6 weeks of STZ, developed elevated level of BUN, protein in urine, urinary output, serum creatinine, serum cholesterol, kidney weight, kidney weight/body weight, and renal cortical collagen content, while serum nitrite/nitrate concentration was significantly decreased as compared to normal control group. Treatment with sodium nitrite (NO donor), l-arginine (NO precursor), daidzein (caveolin inhibitor), and combination of l-arginine and daidzein for 2 weeks markedly attenuated these changes and increased serum nitrite/nitrate ratio. However, treatment with L-NAME, a eNOS inhibitor, significantly attenuated the l-arginine-, daidzein-, or combination of l-arginine and daidzein-induced ameliorative effects in DN. The finding of this study suggests that caveolin plays a vital role in the eNOS-mediated decrease in renal level of NO, which may be responsible for the development of DN in rats.

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Acknowledgments

We are grateful to Mr. Praveen Garg, Chairman ISF College of Pharmacy, Moga for his support and encouragement during the conduct of this study.

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  1. Department of Pharmacology, I.S.F. College of Pharmacy, Ghal Kalan, Moga, 142001, Punjab, India

    Atul Arya, Harlokesh Naryan Yadav & P. L. Sharma

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  1. Atul Arya
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  2. Harlokesh Naryan Yadav
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  3. P. L. Sharma
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Correspondence to Harlokesh Naryan Yadav.

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Arya, A., Yadav, H.N. & Sharma, P.L. Involvement of vascular endothelial nitric oxide synthase in development of experimental diabetic nephropathy in rats. Mol Cell Biochem 354, 57–66 (2011). https://doi.org/10.1007/s11010-011-0805-6

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  • DOI: https://doi.org/10.1007/s11010-011-0805-6

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