Effects of estrogen on blood pressure and salt and water excretion during a ten-day Angiotesin ll infusion period in ovariectomized mice

Abstract

Introduction: Premenopausal women are protected from cardiovascular disease compared to age-matched men. Estrogen (E2) plays important roles in these protective mechanisms.

Purpose: Our goal was to determine if E2 reduces angiotensin II (AngII)-induced elevation in blood pressure in ovariectomized (OVX) mice. We also hypothesized that E2 affects renal excretion of water and sodium.

Methods: Four-week-old CD-1 OVX mice were placed in metabolic cages for a five-day baseline period followed by implantation of an Alzet osmotic pump containing either vehicle or AngII (1 µg/kg/min) and either a placebo or 0.7mg E2 pellet. Measurements of water intake (WI, ml/day), urine volume (UV, ml/day), and urine sodium excretion (UNaE, μEq/day) were recorded daily in the baseline and ten-day post-implantation periods in three groups of mice: vehicle-placebo (V-P), AngII-placebo (AngII-P), and AngII-E2 (n=4/group). Systolic blood pressure (SBP, mmHg) was determined via the tail-cuff technique.

Results: Delta SBP (baseline vs AngII period) was higher in AngII-P but not significantly different from AngII-E2 mice, (33.1±3.5 vs 24.5±4.0, respectively). AngII-E2 mice compared to AngII-P mice had lower WI (4.2±0.02 vs 6.9±0.05, respectively, p<0.001), lower UV (1.3±0.02 vs 2.6±0.03, respectively, p<0.03), and lower UNaE (110.5±20.7 vs 199.7±10.8, respectively, p<0.003).

Conclusion: E2 administration reduces WI, UV, and UNaE during a ten-day AngII-infusion in OVX mice. E2 did not significantly reduce SBP. Studies of longer duration are underway to investigate the important E2-induced mechanisms on blood pressure regulation.