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

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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 (O2·) and hydrogen peroxide (H2O2) 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 O2· and H2O2 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.

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