Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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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PMID:Classical Dendritic Cells Mediate Hypertension by Promoting Renal Oxidative Stress and Fluid Retention. 3178 85