Abstract P185: Hydralazine Treatment Does Not Fully Reduce Proinflammatory Immune Cells In The Ovaries Of Mice With Salt-sensitive Hypertension

Abstract

Salt-sensitive hypertension (SSHTN) is associated with altered macrophage polarization, inflammation, and inflammation-associated lymphangiogenesis in the ovaries of mice, and this is associated with reproductive dysfunction. However, it is unknown whether high pressure or salt or both are involved in these adverse effects. We hypothesized that lowering of blood pressure will not reduce proinflammatory immune cells and inflammation in the ovaries of mice with SSHTN. Female C57BL6/J mice were divided into 3 groups: Control (C) mice received tap water and normal diet; SSHTN mice received L-NAME (0.5 mg/mL) in the drinking water for 2 weeks, followed by a 2-week washout period, and a subsequent 3-week 4% salt diet; and the third group were SSHTN and received hydralazine (250 mg/L) in their drinking water (HYD) during the last 3 weeks of salt diet. There was a significant increase in systolic blood pressure in SSHTN mice (143±2 mm Hg) when compared to control (99±2 mm Hg) but was reduced significantly in HYD mice (119±1 mm Hg). Flow cytometry analysis revealed a significant increase in M1 macrophages in the ovaries of SSHTN and HYD mice when compared to C mice (% of CD45 cells: C: 25%±2, SSHTN: 37.8%±2, HYD: 36.2%±3; p<0.05). There was an increase in CD4+TNFa+IFNg+ Th1 cells in the ovaries of SSHTN and HYD mice when compared to C mice (C: 0.33%±0.06, SSHTN: 0.8%±0.07, HYD: 0.7%±0.1; p<0.05), whereas CD4+ T cells (C: 26.5%±2, SSHTN: 51.5%±4, HYD: 14.7%±3; p<0.05) and CD4+IL17a+ Th17 cells (C: 2.9%±0.2, SSHTN: 5.4%±1, HYD: 3.1%±0.6; p<0.05) significantly increased in SSHTN mice but were reduced in HYD mice. Increased gene expression of IL-17 and iNOS was observed in the ovaries of SSHTN and HYD mice. Together, these data demonstrate that both high blood pressure and salt exert their effect on immune cells differentially contributing to the ovarian dysfunction in SSHTN mice. Further studies are needed to investigate whether manipulating macrophage polarization could reverse these adverse effects in the ovaries of mice with SSHTN.