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

Research output: Contribution to journalArticle

Authors

External Institution(s)

  • Duke University

Details

Original languageEnglish (US)
Pages (from-to)131-138
Number of pages8
JournalHypertension (Dallas, Tex. : 1979)
Volume75
Issue number1
StatusPublished - Jan 1 2020
Peer-reviewedYes

Abstract

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.

    Research areas

  • dendritic cells, diuresis, hypertension, oxidative stress, sodium

Citation formats

APA

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 (Dallas, Tex. : 1979), 75(1), 131-138. https://doi.org/10.1161/HYPERTENSIONAHA.119.13667

Harvard

Lu, X, Rudemiller, NP, Privratsky, JR, Ren, J, Wen, Y, Griffiths, R & Crowley, SD 2020, 'Classical Dendritic Cells Mediate Hypertension by Promoting Renal Oxidative Stress and Fluid Retention', Hypertension (Dallas, Tex. : 1979), vol. 75, no. 1, pp. 131-138. https://doi.org/10.1161/HYPERTENSIONAHA.119.13667