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Classical Dendritic Cells Mediate Hypertension by Promoting Renal Oxidative Stress and Fluid Retention.

Publication ,  Journal Article
Lu, X; Rudemiller, NP; Privratsky, JR; Ren, J; Wen, Y; Griffiths, R; Crowley, SD
Published in: Hypertension
January 2020

FLT3L (Fms-like tyrosine kinase 3 ligand) stimulates the development of classical dendritic cells (DCs). Here we tested the hypothesis that classical DCs drive blood pressure elevation by promoting renal fluid retention. FLT3L-deficient (FLT3L-/-) mice that lack classical DCs in the kidney had mean arterial pressures similar to wild-types (WTs) at baseline but had blunted hypertensive responses during 4 weeks of chronic Ang II (angiotensin II) infusion. In FLT3L-/- mice, the proportions of effector memory T cells in the kidney were similar to those in WTs at baseline. However, after Ang II infusion, proportions of effector memory T cells were dramatically lower in the FLT3L-/- kidneys versus WTs, indicating that classical DCs augment the renal accumulation of effector T cells after renin-angiotensin system activation. Consistent with their lower blood pressures, the Ang II-infused FLT3L-/- mice had attenuated cardiac hypertrophy and lower renal mRNA expression for pro-hypertensive cytokines. Moreover, the Ang II-infused FLT3L-/- mice had lower urinary excretion of the oxidative stress marker 8-isoprostane and lower renal mRNA levels of nicotinamide adenine dinucleotide phosphate oxidase 2. In an intraperitoneal saline challenge test at day 7 of Ang II, FLT3L-/- mice excreted higher proportions of the injected volume and sodium than WTs. Consistent with this enhanced diuresis, mRNA expressions for the sodium chloride cotransporter and all 3 subunits of the epithelial sodium channel were diminished by >40% in FLT3L-/- kidneys compared with the WTs. Thus, classical FLT3L-dependent DCs promote renal T-cell activation with consequent oxidative stress, fluid retention, and blood pressure elevation.

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Published In

Hypertension

DOI

EISSN

1524-4563

Publication Date

January 2020

Volume

75

Issue

1

Start / End Page

131 / 138

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Oxidative Stress
  • Mice, Knockout
  • Mice
  • Membrane Proteins
  • Kidney
  • Hypertension
  • Disease Models, Animal
  • Dendritic Cells
  • Cardiovascular System & Hematology
 

Citation

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Lu, X., Rudemiller, N. P., Privratsky, J. R., Ren, J., Wen, Y., Griffiths, R., & Crowley, S. D. (2020). Classical Dendritic Cells Mediate Hypertension by Promoting Renal Oxidative Stress and Fluid Retention. Hypertension, 75(1), 131–138. https://doi.org/10.1161/HYPERTENSIONAHA.119.13667
Lu, Xiaohan, Nathan P. Rudemiller, Jamie R. Privratsky, Jiafa Ren, Yi Wen, Robert Griffiths, and Steven D. Crowley. “Classical Dendritic Cells Mediate Hypertension by Promoting Renal Oxidative Stress and Fluid Retention.Hypertension 75, no. 1 (January 2020): 131–38. https://doi.org/10.1161/HYPERTENSIONAHA.119.13667.
Lu X, Rudemiller NP, Privratsky JR, Ren J, Wen Y, Griffiths R, et al. Classical Dendritic Cells Mediate Hypertension by Promoting Renal Oxidative Stress and Fluid Retention. Hypertension. 2020 Jan;75(1):131–8.
Lu, Xiaohan, et al. “Classical Dendritic Cells Mediate Hypertension by Promoting Renal Oxidative Stress and Fluid Retention.Hypertension, vol. 75, no. 1, Jan. 2020, pp. 131–38. Pubmed, doi:10.1161/HYPERTENSIONAHA.119.13667.
Lu X, Rudemiller NP, Privratsky JR, Ren J, Wen Y, Griffiths R, Crowley SD. Classical Dendritic Cells Mediate Hypertension by Promoting Renal Oxidative Stress and Fluid Retention. Hypertension. 2020 Jan;75(1):131–138.

Published In

Hypertension

DOI

EISSN

1524-4563

Publication Date

January 2020

Volume

75

Issue

1

Start / End Page

131 / 138

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Oxidative Stress
  • Mice, Knockout
  • Mice
  • Membrane Proteins
  • Kidney
  • Hypertension
  • Disease Models, Animal
  • Dendritic Cells
  • Cardiovascular System & Hematology