title: Sex differences in T-lymphocyte tissue infiltration and development of angiotensin II hypertension.
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.
authors.affiliation: Department of Physiology University of Arizona, Tucson, AZ.|Sarver Heart Center University of Arizona, Tucson, AZ.
authors.forename: Dennis P
authors.initials: DP
authors.lastname: Pollow
authors.affiliation: Department of Immunobiology University of Arizona, Tucson, AZ.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Uhrlaub
authors.affiliation: Department of Physiology University of Arizona, Tucson, AZ.
authors.forename: Melissa
authors.initials: M
authors.lastname: Romero-Aleshire
authors.affiliation: Department of Medicine and Center for the Study of Sex Differences in Health, Aging and Disease, Georgetown University, Washington, DC.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Sandberg
authors.affiliation: Department of Immunobiology University of Arizona, Tucson, AZ.
authors.forename: Janko
authors.initials: J
authors.lastname: Nikolich-Zugich
authors.affiliation: Department of Physiology University of Arizona, Tucson, AZ.|Sarver Heart Center University of Arizona, Tucson, AZ.
authors.forename: Heddwen L
authors.initials: HL
authors.lastname: Brooks
authors.affiliation: Department of Physiology University of Arizona, Tucson, AZ.|Sarver Heart Center University of Arizona, Tucson, AZ.|Evelyn McKnight Brain Institute, University of Arizona, Tucson, AZ.
authors.forename: Meredith
authors.initials: M
authors.lastname: Hay
mesh_terms: D000804:Angiotensin II; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D005260:Female; D006339:Heart Rate; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006973:Hypertension / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012727:Sex Characteristics; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018398:Homeodomain Proteins; D000804:Angiotensin II; C064658:RAG-1 protein
keywords: T-lymphocytes; angiotensin II; hypertension; kidney; sex characteristics; subfornical organ