Abstract 310: 17-β Estradiol Treatment Prevents Angiotensin II-Induced Hypertension in VCD-Treated Menopausal Female Mice, Independent of Renal T Lymphocyte Infiltration
T lymphocytes are required for the development of Angiotensin II (Ang II) hypertension in male mice. Cycling female mice are protected against Ang II hypertension, and inducing ovarian failure (menopause) eliminates this protection. We have previously shown that female Rag-1-/- mice with adoptively transferred T cells have significantly reduced renal T cell infiltration compared to males. Therefore, we hypothesized that an increase in renal T cell infiltration underlies the genesis of hypertension in menopausal female mice. 10 week old C57Bl/6 female mice received ip VCD injections for 20 consecutive days to induce ovarian failure. Cyclicity was monitored daily via vaginal cytology. Once in menopause, an osmotic minipump was implanted, releasing Ang II (800ng/kg/min) for 14 days. In a subset of mice, a 17-β estradiol pellet (0.1mg) was implanted subcutaneously. Upon harvest, T cell infiltration was measured via flow cytometry. Baseline blood pressure was similar among all groups. Ang II infusion elicited a significantly greater increase in MAP in menopausal mice compared to cycling control (Ang Δ11±10mmHg vs Meno/Ang Δ32±6, p<0.05), which was prevented by 17-β estradiol replacement (Meno/Ang/E2 Δ5±2mmHg). Despite elevated MAP, there was no significant increase in renal CD3+, CD4+ or CD8+ T lymphocyte infiltration in Meno/Ang group vs control. However, 17-β estradiol replacement decreased IL-2 renal mRNA expression (0.45±0.13 fold), and increased IL-10 expression (2.41±0.73 fold) compared to Ang II-treated menopausal mice. Ang II induced glomerular hypertrophy in all groups, independent of hormonal status (Control 2156±54μm2 vs. Ang 3970±383*μm2 vs. Meno/Ang 3729±51*μm2 vs. Meno/E2/Ang 3505±71*μm2, *p<0.05 vs. control). These results demonstrate that the enhanced hypertensive response to Ang II in VCD-treated menopausal mice results from the loss of estrogen function, and does not require an increase in renal T lymphocyte infiltration. Ang II-induced glomerular hypertrophy occurs independently of blood pressure or hormonal status. The VCD model of ovarian failure is a useful model for investigating the underlying mechanisms of estrogen’s role in blood pressure regulation.
Author Disclosures: D.P. Pollow: None. J. Romero-Aleshire: None. E. Goldberg: None. J. Nikolich-Zugich: None. H.L. Brooks: None.
- © 2014 by American Heart Association, Inc.