GPER‐1 Agonist Reduces Angiotensin‐II Induced Oxidative Stress in Rat Aortic Smooth Muscle Cells

Abstract

We previously showed that the G protein‐coupled estrogen (GPER) reduces oxidative stress in the kidneys and aorta of female mRen2 rats, a model of angiotensin (Ang) II‐dependent hypertension. The goal of the current study was to assess the mechanisms by which GPER reduces oxidative stress. We hypothesized that GPER activation reduces Ang II‐mediated oxidative stress in rat aortic smooth muscle cells (ASMC) by inhibiting phosphorylation and translocation of Rac1, a small GTPase that recruits subunits to the NADPH oxidase complex. A7r5 cells were treated overnight with either 100 nM of Ang II in the presence of vehicle or 100 nM G‐1. Superoxide levels were measured via electron spin resonance spectroscopy, and RAC and phospho‐RAC were measured via Western blot. Activation of GPER by the agonist G‐1 significantly reduced Ang II‐induced superoxide levels (P<0.05) in AMSC. While there were no significant changes in RAC expression, phospho‐RAC was reduced with G‐1 treatment (P<0.05). We conclude that GPER exerts vascular protection against Ang II‐mediated superoxide production by reducing the phosphorylation of RAC. This anti‐oxidant action of the novel GPER may be one mechanism by which estrogen protects against cardiovascular disease.Support or Funding InformationThis study was funded by National Institutes of Health grant 4R00HL103974 to S.H.L