Effects of the G Protein‐coupled Estrogen Receptor on Cardiovascular Remodeling Induced by Chronic Sympathetic Activation

Abstract

Listen

Translate article

Estrogens modulate cardiovascular function via the classical nuclear hormone receptors ERα and ERβ, and the more recently discovered G protein‐coupled estrogen receptor (GPER). While the activation of GPER elicits many cardioprotective effects, the mechanisms behind these effects are incompletely understood. Sympathetic nervous activities are essential for normal cardiac functions; however, chronic sympathetic activation is an important contributor to maladaptive cardiovascular remodeling that leads to cardiovascular diseases. Our recent data demonstrate that GPER activity moderates the increases in myocardial contraction and calcium dynamics stimulated by acute activation of the cardiac beta1 adrenergic receptor. However, the effects of GPER activation on the cardiac manifestations in response to chronic sympathetic activation are unknown. We hypothesized that GPER activation would reduce cardiovascular remodeling induced by chronic norepinephrine (NE) administration. In adult female ovariectomized mice, administration of NE (10 mg/kg/day) via osmotic pumps for 8 weeks increased heart weight, kidney weight, cardiomyocyte size as assessed by wheat germ agglutinin staining, left ventricular wall thickness, and aorta wall thickness. These changes occurred without an apparent increase in blood pressure assessed by tail cuff measurements. These effects were reduced by the co‐administration of GPER agonist G‐1 (120 mg/kg/day), while administration of G‐1 alone at the same dose had no effect. These initial data indicate that the GPER agonist G‐1 can reduce cardiovascular remodeling caused by chronic sympathetic activation.Support or Funding InformationDMU IOER 05‐19‐06