Effects of Estrogen on Water Intake, Urine Volume, Sodium Excretion, and Blood Pressure During a Ten‐Day Angiotensin II Infusion Period in Ovariectomized Mice

Sex steroids play important roles in blood pressure regulation as well as in other physiological regulatory systems. Although estrogen replacement is thought to prevent or reduce cardiovascular disease in postmenopausal women, conflicting evidence exists as to whether or not estrogen reduces blood pressure. The main purpose of this study was to determine if estrogen administration reduces angiotensin II (Ang II)‐induced increase in blood pressure in ovariectomized (OVX) mice. Four‐week‐old CD‐1 OVX mice were purchased from Envigo Inc. (Indianapolis, IN) and placed in metabolic cages for a five‐day baseline period followed by implantation of an Alzet osmotic pump containing either vehicle or Ang II (1μg/kg/min) and either a placebo or 0.7 mg b‐estradiol (E2) pellet (Innovative Research of America, Sarasota, FL). Measurements were recorded daily in the five‐day baseline and ten‐day post‐implantation periods in three groups of mice: vehicle‐placebo (V‐P), Ang II‐placebo (Ang II‐P), and Ang II‐estrogen (Ang II‐E2) (n=4/group). Mice consumed standard chow and tap water ad libitum throughout the study. Systolic blood pressure (SBP, mmHg) was determined daily via the tail‐cuff technique (CODA, Kent Scientific, Torrington, CT). The delta SBP (baseline vs Ang II periods) was higher in Ang II‐P mice but not significantly different from the Ang II‐E2 mice: (33.1 ± 3.5 vs 24.5 ± 4.0, respectively). Additionally, these values were not significantly different from the delta SBP (30.5 ± 6.1) from intact female (IF) CD‐1 mice under the same Ang II conditions determined in a previous study (Rouch, A. el al. FASEB J, 2018, A 904.6). Using repeated‐measures ANOVA, we found significant effects of E2 on water intake (WI), urine volume (UV), and sodium excretion (UNaE) during the 10‐day post‐implantation period (no differences occurred in the baseline period). E2 appeared to prevent an Ang II‐induced increase in water WI (ml/day): (Ang II‐P vs AngII‐E2; 6.9 ± 0.5 vs 4.2 ± 0.2, p < 0.001). E2 administration resulted in lower UV (ml/day): (Ang II‐P vs Ang II‐E2; 2.6 ± 0.3 vs 1.3 ± 0.2, p<0.03). E2 administration also resulted in lower UNaE (microEq/day): (Ang II‐P vs Ang II‐E2, 199.7 ± 10.8 vs 110.5 ± 20.7, p < 0.003). We conclude that continuous E2 administration via the 0.7 mg E2 pellet affects WI, UV, and UNaE during a ten‐day Ang II infusion period in OVX CD‐1 mice. Moreover, neither the pellet‐induced E2 administration nor endogenous estrogen in IF mice affected the Ang II‐induced increase in blood pressure. Studies of longer duration with more mice/group are underway to investigate mechanistic differences due to E2. Support or Funding Information This project was supported by the National Institute of General Medical Sciences of National Institutes of Health through Grant Number 8P20GM103447. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .