{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T01:43:11Z","timestamp":1792633391805,"version":"4.5.0"},"reference-count":93,"publisher":"American Physiological Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2015,11,15]]},"abstract":"<jats:p>Normal pregnancy is associated with adaptive hemodynamic, hormonal, and vascular changes, and estrogen (E<jats:sub>2<\/jats:sub>) may promote vasodilation during pregnancy; however, the specific E<jats:sub>2<\/jats:sub>receptor (ER) subtype, post-ER signaling mechanism, and vascular bed involved are unclear. We tested whether pregnancy-associated vascular adaptations involve changes in the expression\/distribution\/activity of distinct ER subtypes in a blood vessel-specific manner. Blood pressure (BP) and plasma E<jats:sub>2<\/jats:sub>were measured in virgin and pregnant ( day 19) rats, and the thoracic aorta, carotid artery, mesenteric artery, and renal artery were isolated for measurements of ER\u03b1, ER\u03b2, and G protein-coupled receptor 30 [G protein-coupled ER (GPER)] expression and tissue distribution in parallel with relaxation responses to E<jats:sub>2<\/jats:sub>(all ERs) and the specific ER agonist 4,4\u2032,4\u2033-(4-propyl-[1H]-pyrazole-1,3,5-triyl)-tris-phenol (PPT; ER\u03b1), diarylpropionitrile (DPN; ER\u03b2), and G1 (GPER). BP was slightly lower and plasma E<jats:sub>2<\/jats:sub>was higher in pregnant versus virgin rats. Western blots revealed increased ER\u03b1 and ER\u03b2 in the aorta and mesenteric artery and GPER in the aorta of pregnant versus virgin rats. Immunohistochemistry revealed that the increases in ERs were mainly in the intima and media. In phenylephrine-precontracted vessels, E<jats:sub>2<\/jats:sub>and PPT caused relaxation that was greater in the aorta and mesenteric artery but similar in the carotid and renal artery of pregnant versus virgin rats. DPN- and G1-induced relaxation was greater in the mesenteric and renal artery than in the aorta and carotid artery, and aortic relaxation to G1 was greater in pregnant versus virgin rats. The nitric oxide synthase inhibitor N<jats:sup>\u03c9<\/jats:sup>-nitro-l-arginine methyl ester with or without the cyclooxygenase inhibitor indomethacin with or without the EDHF blocker tetraethylammonium or endothelium removal reduced E<jats:sub>2<\/jats:sub>, PPT, and G1-induced relaxation in the aorta of pregnant rats, suggesting an endothelium-dependent mechanism, but did not affect E<jats:sub>2<\/jats:sub>-, PPT-, DPN-, or G1-induced relaxation in other vessels, suggesting endothelium-independent mechanisms. E<jats:sub>2<\/jats:sub>, PPT, DPN, and G1 caused relaxation of Ca<jats:sup>2+<\/jats:sup>entry-dependent KCl contraction, and the effect of PPT was greater in the mesenteric artery of pregnant versus virgin rats. Thus, during pregnancy, an increase in ER\u03b1 expression in endothelial and vascular smooth muscle layers of the aorta and mesenteric artery is associated with increased ER\u03b1-mediated relaxation via endothelium-derived vasodilators and inhibition of Ca<jats:sup>2+<\/jats:sup>entry into vascular smooth muscle, supporting a role of aortic and mesenteric arterial ER\u03b1 in pregnancy-associated vasodilation. GPER may contribute to aortic relaxation while enhanced ER\u03b2 expression could mediate other genomic vascular effects during pregnancy.<\/jats:p>","DOI":"10.1152\/ajpheart.00532.2015","type":"journal-article","created":{"date-parts":[[2015,9,26]],"date-time":"2015-09-26T01:09:05Z","timestamp":1443229745000},"page":"H1679-H1696","source":"Crossref","is-referenced-by-count":47,"title":["Adaptive increases in expression and vasodilator activity of estrogen receptor subtypes in a blood vessel-specific pattern during pregnancy"],"prefix":"10.1152","volume":"309","author":[{"given":"Karina M.","family":"Mata","sequence":"first","affiliation":[{"name":"Vascular Surgery Research Laboratory, Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Vascular Surgery Research Laboratory, Division 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