title: Oxidative Stress Is Involved in the Renal Dysfunction Induced by Sinoaortic Denervation in Rats.
abstract: The hypothesis that oxidative stress contributes to renal dysfunction in sinoaortically denervated (SAD) rats was investigated. Rats were sinoaortically denervated and received treatment with tempol (0.5 mmol/L in drinking water) for 8 weeks. Although the tempol treatment of the SAD rats had no significant effect on blood pressure or blood pressure viability, it significantly ameliorated the renal dysfunction as indicated by increases in renal blood flow (RBF) and the glomerular filtration rate (GFR) and reductions in plasma creatinine, blood urea nitrogen (BUN), the urine albumin excretion rate (UAE), and the glomerular sclerosis score (GSS). The SAD rats treated with tempol exhibited decreased plasma and renal malondialdehyde (MDA) levels and reduced renal formation of reactive oxygen species (ROS), superoxide (O2-), peroxynitrite (OONO-) and 3-nitrotyrosine. Treatment with tempol suppressed the nuclear concentration of nuclear factor-kappaB (NF-κB) and reduced the renal levels of macrophage chemoattractant protein 1 (MCP-1) and interleukin-6 (IL-6). The tempol-treated SAD rats exhibited decreased renal advanced glycation end product (AGE) levels and decreased receptor for advanced glycation end products (RAGE) protein expression. The tempol treatment of the SAD rats restored mitochondrial adenosine triphosphate (ATP) formation, DNA content, membrane integrity and the renal oxygen consumption rate. Additionally, the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione S epoxide transferase (GST), and catalase were decreased, and the activities of xanthin oxidase (XO) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase were enhanced in the kidneys of the SAD rats. In conclusion, our work firstly provided direct evidence that oxidative stress played an important role in the renal dysfunction of SAD rats.
authors.affiliation: Clinical Pharmacy Laboratory, PLA Greneral Hospital.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.forename: Jiao
authors.initials: J
authors.lastname: Fan
authors.forename: Dong
authors.initials: D
authors.lastname: Chai
authors.forename: Minghua
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017763:Autonomic Denervation / Q000009:adverse effects*; D003497:Cyclic N-Oxides / Q000627:therapeutic use; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism*; D013113:Spin Labels
chemical_list: D003497:Cyclic N-Oxides; D013113:Spin Labels; C001803:tempol