Vitamin E reduces glomerulosclerosis, restores renal neuronal NOS, and suppresses oxidative stress in the 5/6 nephrectomized rat.
Chronic kidney disease is accompanied by nitric oxide (NO) deficiency and oxidative stress, which contribute to progression. We investigated whether the antioxidant vitamin E could preserve renal function and NO bioavailability and reduce oxidative stress in the 5/6th nephrectomy (NX) rat model. We studied the following three groups of male Sprague-Dawley rats: sham (n = 6), 5/6 NX control (n = 6), and 5/6 NX treated with vitamin E (5,000 IU/kg chow; n = 5). The 5/6 NX group showed increased severity of glomerulosclerosis vs. sham, and this was ameliorated by vitamin E therapy. Both 5/6 NX groups showed similar elevations in plasma creatinine and proteinuria and decreased 24-h creatinine clearance compared with sham. There was increased NADPH-dependent superoxide production in 5/6 NX rats vs. sham that was prevented by vitamin E. Total NO production was similarly reduced in both 5/6 NX groups. There was unchanged abundance of endothelial nitric oxide synthesis (NOS) in renal cortex and medulla and neuronal (n) NOS in medulla. However, in kidney cortex, 5/6 NX rats had lower nNOS abundance than sham, which was restored by vitamin E. An increased plasma asymmetric dimethylarginine occurred with 5/6 NX associated with decreased renal dimethylarginine dimethylaminohydrolase activity and increased type 1 protein arginine methyltransferase expression.
Tain
You-Lin
YL
Department of Physiology and Functional Genomics, University of Florida, Gainesville, Florida, USA. tainyl@ufl.edu
Freshour
Gary
G
Dikalova
Anna
A
Griendling
Kathy
K
Baylis
Chris
C
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003404:Creatinine / Q000097:blood; D018450:Disease Progression; D005923:Glomerulosclerosis, Focal Segmental / Q000150:complications / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D007668:Kidney / Q000201:enzymology*; D008297:Male; D009249:NADP / Q000378:metabolism; D009392:Nephrectomy / Q000379:methods; D009569:Nitric Oxide / Q000096:biosynthesis; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011507:Proteinuria / Q000209:etiology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology*
D000975:Antioxidants; D013481:Superoxides; D014810:Vitamin E; D009569:Nitric Oxide; D009249:NADP; D003404:Creatinine; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III