Tumor necrosis factor-α antagonist etanercept decreases blood pressure and protects the kidney in a mouse model of systemic lupus erythematosus

Marcia Venegas-Pont, Michaele B. Manigrasso, Samira C. Grifoni, Babbette B. Lamarca, Christine Maric, Lorraine C. Racusen, Porter H. Glover, Allison V. Jones, Heather A. Drummond, Michael J. Ryan

Research output: Contribution to journalArticle

Abstract

Chronic inflammation has been implicated in the pathology of hypertension; however, the role for specific cytokines remains unclear. We tested whether tumor necrosis factor-α blockade with etanercept (Etan) reduces mean arterial pressure in a female mouse model of systemic lupus erythematosus (SLE). SLE is a chronic inflammatory disorder with prevalent hypertension. Thirty-week-old SLE (NZBWF1) and control mice (NZW/LacJ) received Etan (0.8 mg/kg SC weekly) for 4 weeks or vehicle. Mean arterial pressure (in millimeters of mercury) was increased in SLE mice (150±5 versus 113±5 in controls; P<0.05) and was lower in Etan-treated SLE mice (132±3) but not controls (117±5). Albuminuria (in micrograms per milligram of creatinine) was elevated in SLE mice (28 742±9032 versus 1075±883; P<0.05) and was lower in Etan-treated SLE mice (8154±3899) but not control animals (783±226). Glomerulosclerosis (in percentage of glomeruli) was evident in SLE mice (2.5±1.6 versus 0.0±0.0 in controls; P<0.05) and was ameliorated in Etan-treated SLE mice (0.1±0.1). Renal cortex CD68 cell staining (in percentage of area) was elevated in SLE mice (4.75±0.80 versus 0.79±0.12 in controls; P<0.05) and was lower in Etan-treated SLE mice (2.28±0.32) but not controls (1.43±0.25). Renal cortex NADPH oxidase activity (relative light units per milligram of protein) was higher in SLE mice compared with controls (10 718±1276 versus 7584±229; P<0.05) and lowered in Etan-treated SLE mice (6645±490). Renal cortex nuclear factor κB (phosphorylated and nonphosphorylated) was increased in SLE mice compared with controls and lower in Etan-treated SLE mice. These data suggest that TNF-α mechanistically contributes to the development of hypertension in a chronic inflammatory disease through increased renal nuclear factor κB, oxidative stress, and inflammation.

Original languageEnglish (US)
Pages (from-to)643-649
Number of pages7
JournalHypertension
Volume56
Issue number4
DOIs
StatePublished - Oct 1 2010

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Keywords

  • TNF-α
  • cytokine
  • hypertension
  • inflammation
  • oxidative stress
  • systemic lupus erythematosus

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Venegas-Pont, M., Manigrasso, M. B., Grifoni, S. C., Lamarca, B. B., Maric, C., Racusen, L. C., Glover, P. H., Jones, A. V., Drummond, H. A., & Ryan, M. J. (2010). Tumor necrosis factor-α antagonist etanercept decreases blood pressure and protects the kidney in a mouse model of systemic lupus erythematosus. Hypertension, 56(4), 643-649. https://doi.org/10.1161/HYPERTENSIONAHA.110.157685