Abstract P140: Impact Of Ovariectomy On Aldosterone And Blood Pressure In Lysine-Specific Demethylase 1 (LSD1) Deficient Mice

Abstract

LSD1 regulates steroid receptor function including estrogen and mineralocorticoid receptor. Women of African descent who carry the LSD1 risk allele rs587168 develop salt-sensitive hypertension and aldosterone (ALDO) dysregulation. This phenotype is observed in women above the age of 50 but not below the age of 50, which raises the question whether ovarian function affects the relationship between blood pressure (BP) and LSD1. Therefore, we hypothesized that ovariectomized (OVX) LSD1 +/– female mice will exhibit higher systolic BP (SBP) on liberal salt (LibS) diet as compared to intact LSD1 +/– female littermates. OVX was performed at 40 weeks of age, animals were fully acclimated to tail-cuff BP measurements, and BP was assessed on a LibS diet (1.6% NaCl Purina Chow) at 65 weeks of age, followed by euthanasia of animals and tissue collection. OVX females exhibited lower uterine weight (OVX LSD1 +/– 0.1 ± 0.03 g vs intact LSD1 +/– 0.2 ± 0.02 g, P =0.013) demonstrating OVX was successful. On a LibS diet, 24-h urinary Na + was similar between groups (OVX LSD1 +/– 0.37 ± 0.07 mEq vs intact LSD1 +/– 0.42 ± 0.09 mEq, P =0.678). OVX females exhibited higher SBP (OVX LSD1 +/– 121.5 ± 4.1 mmHg vs intact LSD1 +/– 107.8 ± 4.4 mmHg, P =0.033). 24-h urinary ALDO corrected for urinary creatinine was lower (OVX LSD1 +/– 29.2 ± 2.0 pg/mcg vs intact LSD1 +/– 59.8 ± 7.6 pg/mcg, P <0.001), consistent with a volume expanded state. In Conclusion, OVX increased BP in LSD1 +/- mice, likely related to a mineralocorticoid receptor-mediated volume expansion. This raises the possibility that the reason younger women (<50 years) with LSD1 risk allele do not have salt-sensitive BP is related to ovarian hormones.