Abstract 514: Females are Protected from Hypertension and Kidney and Brain Infiltration of T Lymphocytes During Angiotensin II Infusion
There is extensive evidence that activation of the immune system is both necessary and required for the development of Ang II induced hypertension in males and that the central nervous system (CNS) is involved in this response. The purpose of the present study was to determine if there are sex differences in ability of the adaptive immune system to induce Ang II hypertension and the effect of sex on T-cell infiltration into the brain and kidney during Ang II induced hypertension. Rag-1-/- mice, with a genetic deletion of the recombinase-activating gene and lacking both T and B cells were used in this study. Male (n=4) and female (n=4) Rag-1-/- mice both received adoptive transfer of male CD3+ T cells three weeks prior to 14 day Ang II infusion (490 ng/kg/min). Blood pressure was monitored non-invasively via tail cuff. In Rag-1-/- mice, in the absence of T cells, male and female mean arterial pressure (MAP) responses to Ang II were similar, males increased MAP 14.6 mmHg (107.8mmHg to122.5mmHg) and females increased 14.4 mmHg (102.7mmHg to 117.2 mmHg). However, following adoptive transfer of male CD3+ Tcells, Ang II induced a significantly greater increase in blood pressure in males (delta 37.8 mmHg, 107.2mmHg to 139.5mmHg, p<.05) while female mice had similar changes as seen in controls (delta 16.7 mmHg, 110.1mmHg to126.8mmHg). Flow cytometric analysis of CD3+, CD3+CD4+, CD3+CD4+Foxp3 and CD3+CD8+, lymphocyte surface markers from Rag-1-/- males and females was performed on whole blood, splenic, renal and brain tissue. Absolute CD3+ T cell count from spleen suggested that both sexes had equal T cells engraftment. Males had significantly greater numbers of CD3+CD4+, CD3+CD4+Foxp3 and CD3+CD8+ lymphocyte infiltration of the kidney compared to females in both control and AngII infused animals (p<0.05 comparison of males to females). Males also had significantly increased CD3+CD4+ brain infiltration relative to females. These results suggest that intact female Rag-1-/- mice during Ang II infusion are protected from the hypertensive effects of CD3+ male T cell adoptive transfer as compared to their male counterparts and this protection may involve sex differences in T cell infiltration of the kidney and brain.
- © 2013 by American Heart Association, Inc.