Classical Dendritic Cells Mediate Hypertension by Promoting Renal Oxidative Stress and Fluid Retention
| Autor: | Xiaohan Lu, Yi Wen, Steven D. Crowley, Jamie R. Privratsky, Jiafa Ren, Robert Griffiths, Nathan P. Rudemiller |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Epithelial sodium channel medicine.medical_specialty T-Lymphocytes Sodium medicine.medical_treatment chemistry.chemical_element Diuresis 030204 cardiovascular system & hematology Kidney medicine.disease_cause Article Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine Internal Medicine medicine Animals Saline Mice Knockout Angiotensin II Membrane Proteins Dendritic Cells Disease Models Animal Oxidative Stress 030104 developmental biology medicine.anatomical_structure Endocrinology chemistry Hypertension Oxidative stress Nicotinamide adenine dinucleotide phosphate |
| Zdroj: | Hypertension |
| ISSN: | 1524-4563 0194-911X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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