Sex differences in blood pressure control: are T lymphocytes the missing link?

There is an ever expanding literature base implicating T lymphocytes in the development and progression of numerous cardiovascular diseases, including hypertension. T lymphocytes contribute to the development of hypertension in genetic, angiotensin II (Ang-II), and salt-sensitive male experimental animals. Among the most definitive studies implicating T lymphocytes in hypertension are studies conducted in Rag-1 mice, which lack B and T lymphocytes. Guzik et al were the first to demonstrate that these mice have a blunted hypertensive response to Ang-II infusion. Adoptive transfer of T lymphocytes into male Rag mice restored the hypertensive response to Ang-II; adoptive transfer of B lymphocytes did not alter the blood pressure (BP) response. Although lowgrade inflammation, and T lymphocytes in particular, are now a recognized hallmark of hypertension, the majority of basic science literature in this field has been conducted exclusively in males, despite the fact that females account for ≈50% of all hypertensive cases in the United States. Therefore, it was with great interest that we read the study by Pollow et al in the current issue of Hypertension, which was designed to determine (1) whether there are sex differences in the ability of T lymphocytes to induce Ang-II–dependent hypertension and (2) whether sex affects central or renal T lymphocytes infiltration after Ang-II hypertension. Of particular interest, they found that male mice exhibited a significant increase in BP and renal damage to Ang-II after the adoptive transfer of CD3 T lymphocytes from wild-type male mice. In contrast, BP responses and renal injury to Ang-II were not significantly altered in female Rag mice after adoptive transfer of T lymphocytes from males. Male Rag mice also had greater renal CD3, CD4, CD8, and T-regulatory cells (Tregs) after adoptive transfer than female Rag mice, despite both sexes having comparable BPs, although Ang-II did not significantly affect renal T-lymphocyte infiltration in either sex. Although this may call into question the role of T lymphocytes in Ang-II hypertension in the Rag mice, male mice did express increased mRNA for the inflammatory cytokines interleukin-2, monocyte chemoattractant protein-1, and tumor