Sex differences in T-lymphocyte tissue infiltration and development of Angiotensin II Hypertension

Dennis P. Pollow, Jennifer Uhrlaub, Melissa J. Romero-Aleshire, Kathryn Sandberg, Janko Nikolich-Zugich, Heddwen L. Brooks, Meredith Hay

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

There is extensive evidence that activation of the immune system is both necessary and required for the development of angiotensin II (Ang II)-induced hypertension in males. The purpose of this study was to determine whether sex differences exist in the ability of the adaptive immune system to induce Ang II-dependent hypertension and whether central and renal T-cell infiltration during Ang II-induced hypertension is sex dependent. Recombinant activating gene-1 (Rag-1) mice, lacking both T and B cells, were used. Male and female Rag-1 mice received adoptive transfer of male CD3 T cells 3 weeks before 14-day Ang II infusion (490 ng/kg per minute). Blood pressure was monitored via tail cuff. In the absence of T cells, systolic blood pressure responses to Ang II were similar between sexes (Δ22.1 mm Hg males versus Δ18 mm Hg females). After adoptive transfer of male T cells, Ang II significantly increased systolic blood pressure in males (Δ37.7 mm Hg; P<0.05) when compared with females (Δ13.7 mm Hg). Flow cytometric analysis of total T cells and CD4, CD8, and regulatory Foxp3-CD4 T-cell subsets identified that renal lymphocyte infiltration was significantly increased in males versus females in both control and Ang II-infused animals (P<0.05). Immunohistochemical staining for CD3-positive T cells in the subfornical organ region of the brain was increased in males when compared with that in females. These results suggest that female Rag-1 mice are protected from male T-cell-mediated increases in Ang II-induced hypertension when compared with their male counterparts, and this protection may involve sex differences in the magnitude of T-cell infiltration of the kidney and brain.

Original languageEnglish (US)
Pages (from-to)384-390
Number of pages7
JournalHypertension
Volume64
Issue number2
DOIs
StatePublished - Aug 2014

Keywords

  • T-lymphocytes
  • angiotensin II
  • hypertension
  • kidney
  • sex characteristics
  • subfornical organ

ASJC Scopus subject areas

  • Internal Medicine

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