Role of Estradiol Receptor Beta (ERβ) on Arterial Pressure, Respiratory Chemoreflex and Mitochondrial Function in Young and Aged Female Mice

Abstract

We tested the hypothesis that ERβ is involved in respiratory control in female mice. We used young adult (5–6 months-old) and aged (17–18 months-old) ERβKO or wild-type controls (WT) female mice to assess arterial blood pressure (via a tail-cuff sensor) and indices of respiratory pattern (sighs and apneas – recorded by whole body plethysmography at rest). We also measured respiratory parameters at rest and in response to brief (<10 min) exposure to hypoxia (12% O2) or hypercapnia (5% CO2). Because ERβ is localized in mitochondria, and because estradiol and ERβ agonist increase mitochondrial O2 consumption, we assessed the mitochondrial respiration (with a high-resolution oxygraph system) and the in vitro activity of the complex I of the electron transfer chain in samples of brain cortex in aged wild-type and ERβKO female mice. Compared to young WT mice, young ERβKO mice had elevated arterial blood pressure, but similar ventilatory responses to hypoxia and hypercapnia. In old ERβKO female mice compared to old WT mice, the arterial blood pressure was lower, the frequency of sighs was higher and the frequency of apneas was lower, and the hypoxic and hypercapnic ventilatory responses were reduced. In old ERβKO mice mitochondrial respiration and complex I activities in the brain cortex were lower than in WT mice. We conclude that ERβ has age-specific effects on vascular and respiratory functions in female mice.