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Activated Immune Cells Exacerbate Angiotensin II Induced Hypertension and Renal Damage in the Dahl Salt Sensitive Rat
Author(s) -
Wade Brittany M,
Mattson David
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.964.3
Subject(s) - medicine , endocrinology , angiotensin ii , immune system , recombination activating gene , kidney , excretion , renin–angiotensin system , blood pressure , chemistry , immunology , gene , biochemistry , recombination
In recent years, there has been a reenergized interest in the role of immune cells in the pathogenesis of hypertension. We recently demonstrated attenuated Angiotensin II (AngII) induced hypertension and renal damage in Dahl Salt Sensitive (SS) rats lacking T‐ and B‐ lymphocytes due to a null mutation in the Rag1 gene (SS‐Rag1 em1Mcwi ). The present study was performed to analyze the abundance of different renal infiltrating immune cells and assess the cytokines produced by these cells during AngII induced hypertension. The continuous infusion of AngII (5 ng/kg/min, iv) to SS and SS‐Rag1 em1Mcwi rats fed low salt (0.4% NaCl) chow led to a significantly greater increase in mean arterial pressure (MAP) in SS rats (189±3 mmHg) than in Rag1 mutant rats (177±3 mmHg) after 12 days of infusion (n=9 rats/group). Renal damage, as assessed by albumin excretion rate, was significantly increased after 12 days of AnglI infusion in the SS (from 33±4 to 81±9 mg/day) and in the Rag1 mutants (from 12±2 to 50±8 mg/day); albumin excretion rate was significantly different between the groups at all points measured. To examine the immune cells involved in the phenotypic response of the SS rats, cells were isolated from the kidneys and analyzed by flow cytometry. Compared to vehicle infused rats, kidneys of AngII treated SS rats had increased CD45+ total leukocytes (1,807,134±235,766 vs. 4,434,147±1,295,814 cells/kidney), CD11b/c+ macrophages/monocytes (1,439,002±163,119 vs. 3,566,048±1,124,655 cells/kidney), and CD3+ T Cells (299,557±81,501 vs. 740,370±155,065 cells/kidney). Further experiments were performed to assess the abundance of cytokine secreting CD3+ cells in the kidneys of AngII and vehicle infused SS rats. These experiments revealed 57% more CD3+/IL17+ T cells from the rats treated with AngII than the vehicle infused group (n=5–6 rats/group). This difference in IL‐17 production was observed in both CD3+/CD4+ and CD3+/CD8+ T cells. There was a tendency for more CD3+/IFNγ and CD3+/TNFα cells from the AngII infused group as well, though the changes were not significant. The present data suggest that infiltrating T cells in the kidney may secrete IL17 or other cytokines to exacerbate renal damage in AngII induced hypertension. Support or Funding Information Supported by DK‐96859 and HL116264