Renal Tumor Necrosis Factor α Contributes to Hypertension in Dahl Salt-Sensitive Rats

Baorui Huang, Yuan Cheng, Kristie Usa, Yong Liu, Maria Angeles Baker, David L. Mattson, Yongcheng He, Niansong Wang, Mingyu Liang

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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.13BN26 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.

Original languageEnglish (US)
Article number21960
JournalScientific reports
Volume6
DOIs
StatePublished - Feb 26 2016
Externally publishedYes

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    Huang, B., Cheng, Y., Usa, K., Liu, Y., Baker, M. A., Mattson, D. L., He, Y., Wang, N., & Liang, M. (2016). Renal Tumor Necrosis Factor α Contributes to Hypertension in Dahl Salt-Sensitive Rats. Scientific reports, 6, [21960]. https://doi.org/10.1038/srep21960