T cell‐dependent hypertension is attenuated in female mice during angiotensin II infusion (1136.10)

Abstract

Previous studies have shown that the adaptive immune system is required for the development of Ang II‐induced hypertension in male mice. Here we determine if there are sex differences in the ability of the adaptive immune system to induce hypertension and alter T cell infiltration and renal dysfunction in response to Ang II infusion. Male and female RAG‐1‐/‐ mice, which lack both T and B cells, received adoptive transfer of male CD3+ T cells 3 weeks prior to Ang II infusion (490ng/kg/min 14d) (n=8). Controls received T cells or Ang II. Blood pressure was monitored via tail cuff. In the absence of T cells, Ang II induced a small increase in systolic blood pressure (SBP) in males & females (Δ10.9 vs. Δ14.1mmHg). After adoptive transfer, Ang II induced a significant increase in SBP in males (Δ36.8mmHg, p< 0.01), while females were no different from Ang II‐only controls (Δ16.9mmHg). PAS staining identified that Ang II infusion significantly increased glomerular hypertrophy in both males and females, independent of T cells; glomerular area was significantly greater in males vs females, at baseline. Renal CD3+, CD4+, CD8+, and Foxp3+ lymphocyte infiltration was significantly greater in males compared to females, independent of Ang II. These results suggest that females are protected from Ang II‐induced T cell‐dependent hypertension, and that this protection may involve sex differences in T cell‐infiltration of the kidney.Grant Funding Source: Supported by Training Grant HL007249 (J. Burt), UA Sarver Heart Center, ARCS Foundation