title: Involvement of vascular endothelial nitric oxide synthase in development of experimental diabetic nephropathy in rats.
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.
authors.affiliation: Department of Pharmacology, I.S.F. College of Pharmacy, Ghal Kalan, Moga, 142001 Punjab, India.
authors.forename: Atul
authors.initials: A
authors.lastname: Arya
authors.forename: Harlokesh Naryan
authors.initials: HN
authors.lastname: Yadav
authors.forename: P L
authors.initials: PL
authors.lastname: Sharma
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001786:Blood Glucose / Q000187:drug effects; D001806:Blood Urea Nitrogen; D001835:Body Weight; D051242:Caveolin 1 / Q000037:antagonists & inhibitors; D002784:Cholesterol / Q000097:blood; D003094:Collagen / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000503:physiopathology*; D004041:Dietary Fats; D004730:Endothelium, Vascular / Q000378:metabolism*; D007529:Isoflavones / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D009573:Nitrites / Q000097:blood; D009929:Organ Size; D011507:Proteinuria; D051381:Rats; D017208:Rats, Wistar; D012977:Sodium Nitrite / Q000494:pharmacology; D014556:Urine
chemical_list: D001786:Blood Glucose; C495537:Cav1 protein, rat; D051242:Caveolin 1; D004041:Dietary Fats; D007529:Isoflavones; D009573:Nitrites; C004742:daidzein; D003094:Collagen; D001120:Arginine; D002784:Cholesterol; D003404:Creatinine; D052250:Nitric Oxide Synthase Type III; D012977:Sodium Nitrite