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Physiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The protective effect of estrogen on the vasculature cannot be explained only by its action through the receptors ER\u03b1 and ER\u03b2. G protein-coupled estrogen receptors (GPER)\u2014which are widely distributed throughout the cardiovascular system\u2014may also be involved in this response. However, little is known about GPER actions in hypertension. Therefore, in this study we evaluated the vascular response mediated by GPER using a specific agonist, G-1, in spontaneously hypertensive rats (SHR). We hypothesized that G-1 would induce a relaxing response in resistance mesenteric arteries from SHR of both sexes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>G-1 concentration-response curves (1 nM-10 \u03bcM) were performed in mesenteric arteries from SHR of both sexes (10\u201312-weeks-old, weighing 180\u2013250 g). The effects of G-1 were evaluated before and after endothelial removal and incubation for 30 min with the inhibitors L-NAME (300 \u03bcM) and indomethacin (10 \u03bcM) alone or combined with clotrimazole (0.75 \u03bcM) or catalase (1,000 units\/mL). GPER immunolocalization was also investigated, and vascular hydrogen peroxide (H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>) and ROS were evaluated using dichlorofluorescein (DCF) and dihydroethidium (DHE) staining, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>GPER activation promoted a similar relaxing response in resistance mesenteric arteries of female and male hypertensive rats, but with the participation of different endothelial mediators. Males appear to be more dependent on the NO pathway, followed by the H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> pathway, and females on the endothelium and H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings show that the GPER agonist G-1 can induce a relaxing response in mesenteric arteries from hypertensive rats of both sexes in a similar way, albeit with differential participation of endothelial mediators. These results contribute to the understanding of GPER activation on resistance mesenteric arteries in essential hypertension.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphys.2021.659291","type":"journal-article","created":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T18:25:18Z","timestamp":1627583118000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Sex Differences in the Vasodilation Mediated by G Protein-Coupled Estrogen Receptor (GPER) in Hypertensive Rats"],"prefix":"10.3389","volume":"12","author":[{"given":"Nathalie Trist\u00e3o Banhos","family":"Delgado","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wender do Nascimento","family":"Rouver","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leandro Ceotto","family":"Freitas-Lima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ildernandes","family":"Vieira-Alves","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Virg\u00ednia Soares","family":"Lemos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger Lyrio dos","family":"Santos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e73562","DOI":"10.1371\/journal.pone.0073562","article-title":"Paraquat poisoning induces TNF-\u03b1-dependent iNOS\/NO mediated hyporesponsiveness of the aorta to vasoconstrictors in rats.","volume":"8","author":"Aires","year":"2013","journal-title":"PLoS One"},{"key":"B2","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.maturitas.2014.04.002","article-title":"Vasodilatory effects of the selective GPER agonist G-1 is maximal in arteries of postmenopausal women.","volume":"78","author":"Arefin","year":"2014","journal-title":"Maturitas"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e56","DOI":"10.1161\/CIR.0000000000000659","article-title":"Heart disease and stroke statistics-2019 update: a report from the american heart association.","volume":"139","author":"Benjamin","year":"2019","journal-title":"Circulation"},{"key":"B4","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1038\/nchembio775","article-title":"Virtual and biomolecular screening converge on a selective agonist for GPR30.","volume":"2","author":"Bologa","year":"2006","journal-title":"Nat. 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