Megan A Sylvester, Dennis P Pollow Jr, Caitlin Moffett, Wendy Nunez, Jennifer L Uhrlaub, Janko Nikolich-Zugich, Heddwen L Brooks

Jan 10, 2022
American Journal of Physiology - Renal Physiology

Premenopausal females are protected from Angiotensin II (Ang II)-induced hypertension following the adoptive transfer of T cells from normotensive donors. For the present study, we hypothesized that the transfer of hypertensive T cells (HT) or splenocytes (HS) from hypertensive donors would eliminate premenopausal protection from hypertension. Premenopausal Rag-1-/- females received either normotensive (NT) or hypertensive cells, three weeks prior to Ang II infusion (14 days, 490 ng/kg/min). Contrary to our hypothesis, no increase in Ang II-induced blood pressure was observed in the NT/Ang or HT/Ang groups. Flow cytometry demonstrated that renal FoxP3+ T regulatory cells were significantly decreased and IHC showed an increase in renal F4/80+ macrophages in HT/Ang, suggesting a shift in the renal inflammatory environment despite no change in blood pressure. Renal mRNA expression of MCP-1, Endothelin-1, GPER-1 were significantly decreased in HT/Ang. The adoptive transfer of hypertensive splenocytes prior to Ang II infusion (HS/Ang) eliminated premenopausal protection from hypertension and significantly decreased splenic FoxP3+ T regulatory cells compared to females receiving normotensive splenocytes (NS/Ang). Expression of MIP-1a/CCL3, a potent macrophage chemokine was elevated in HS/Ang, however no increase in renal macrophage infiltration occurred. Together, these data show that in premenopausal females T cells from hypertensive donors are not sufficient to induce a robust Ang II mediated hypertension, in contrast, transfer of hypertensive splenocytes (consisting of T/B lymphocytes, dendritic cells, macrophages) is sufficient. Further work is needed to understand how innate and adaptive immune cells and estrogen signaling coordinate to cause differential hypertensive outcomes in premenopausal females.

Please Log In to leave a comment.