title: Renal Tumor Necrosis Factor α Contributes to Hypertension in Dahl Salt-Sensitive Rats.
abstract: Tumor necrosis factor α (TNFα) is a major proinflammatory cytokine and its level is elevated in hypertensive states. Inflammation occurs in the kidneys during the development of hypertension. We hypothesized that TNFα specifically in the kidney contributes to the development of hypertension and renal injury in Dahl salt-sensitive (SS) rats, a widely used model of human salt-sensitive hypertension and renal injury. SS rats were chronically instrumented for renal interstitial infusion and blood pressure measurement in conscious, freely moving state. Gene expression was measured using real-time PCR and renal injury assessed with histological analysis. The abundance of TNFα in the renal medulla of SS rats, but not the salt-insensitive congenic SS.13(BN26) rats, was significantly increased when rats had been fed a high-salt diet for 7 days (n = 6 or 9, p < 0.01). The abundance of TNFα receptors in the renal medulla was significantly higher in SS rats than SS.13(BN26) rats. Renal interstitial administration of Etanercept, an inhibitor of TNFα, significantly attenuated the development of hypertension in SS rats on a high-salt diet (n = 7-8, p < 0.05). Glomerulosclerosis and interstitial fibrosis were also significantly ameliorated. These findings indicate intrarenal TNFα contributes to the development of hypertension and renal injury in SS rats.
authors.affiliation: Department of Nephrology and Rheumatology, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, P.R.China.|Medical College of Soochow University, Suzhou, Jiangsu, P.R.China.|Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Baorui
authors.initials: B
authors.lastname: Huang
authors.affiliation: Center of Systems Molecular Medicine, Milwaukee, WI, USA.|Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.|Department of Nephrology, Shenzhen Second People's Hospital and the First Affiliated Hospital of Shenzhen University, Shenzhen, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Center of Systems Molecular Medicine, Milwaukee, WI, USA.|Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Kristie
authors.initials: K
authors.lastname: Usa
authors.affiliation: Center of Systems Molecular Medicine, Milwaukee, WI, USA.|Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Center of Systems Molecular Medicine, Milwaukee, WI, USA.|Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Maria Angeles
authors.initials: MA
authors.lastname: Baker
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Mattson
authors.affiliation: Department of Nephrology, Shenzhen Second People's Hospital and the First Affiliated Hospital of Shenzhen University, Shenzhen, China.
authors.forename: Yongcheng
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Nephrology and Rheumatology, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, P.R.China.
authors.forename: Niansong
authors.initials: N
authors.lastname: Wang
authors.affiliation: Center of Systems Molecular Medicine, Milwaukee, WI, USA.|Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Mingyu
authors.initials: M
authors.lastname: Liang
mesh_terms: D000818:Animals; D015870:Gene Expression; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology; D008297:Male; D023421:Models, Animal; D051381:Rats; D020303:Rats, Inbred Dahl; D017673:Sodium Chloride, Dietary / Q000009:adverse effects*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D017673:Sodium Chloride, Dietary; D014409:Tumor Necrosis Factor-alpha