Sex difference in GPER expression does not change vascular relaxation or reactive oxygen species generation in rat mesenteric resistance arteries.

AIM

An imbalance between antioxidant and pro-oxidant factors, with a predominance of the latter, characterises oxidative stress and is indicative of a loss of vascular function. The beneficial vascular effects of oestrogen may be related to its ability to stimulate the G protein-coupled oestrogen receptor (GPER) and produce antioxidant activity. This study evaluated the GPER-dependent relaxation response in the mesenteric resistance arteries of female and male rats and measured the contributions of pro-oxidant and antioxidant enzymes in this response.

MAIN METHODS

The relaxation response was characterised in third-order mesenteric arteries using concentration-response curves of the selective GPER agonist G-1 (1 nM-10 μM), target protein levels were measured using Western blots, and vascular superoxide anion (O) and hydrogen peroxide (HO) levels were measured using dihydroethidium (DHE) and dichlorofluorescein (DCF) staining, respectively.

KEY FINDINGS

The GPER agonist induced concentration-dependent vasorelaxation without showing differences between sexes. However, GPER expression was greater in male rats. No sex differences were detected in the expression of antioxidant proteins (catalase, SOD-1, and SOD-2). The basal vascular production of O and HO was similar in the studied groups, and stimulation with G-1 maintained this response.

SIGNIFICANCE

Together, our results show that the expression of GPER is greater in male mesenteric arteries, despite of the lack of a difference in vascular response. Nevertheless, antioxidant enzyme expression levels and the generation rates of pro-oxidants were similar between the studied groups. These results offer a new perspective for understanding GPER expression and functionality in resistance arteries.