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Herein, we show that endothelial cell\u2013specific (EC-specific) EP4 gene\u2013knockout mice (EC-EP4\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    ) exhibited elevated, while EC-specific EP4-overexpression mice (EC-hEP4\n                    <jats:sup>OE<\/jats:sup>\n                    ) displayed reduced, BP levels compared with the control mice under both basal and high-salt diet\u2013fed conditions. The altered BP was completely abolished by treatment with l\u2013\n                    <jats:italic>N<\/jats:italic>\n                    <jats:sup>G<\/jats:sup>\n                    -nitro-l-arginine methyl ester (l-NAME), a competitive inhibitor of endothelial nitric oxide synthase (eNOS). The mesenteric arteries of the EC-EP4\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    mice showed increased vasoconstrictive response to angiotensin II and reduced vasorelaxant response to acetylcholine, both of which were eliminated by l-NAME. Furthermore, EP4 activation significantly reduced BP levels in hypertensive rats. Mechanistically, EP4 deletion markedly decreased NO contents in blood vessels via reducing eNOS phosphorylation at Ser1177. EP4 enhanced NO production mainly through the AMPK pathway in cultured ECs. Collectively, our findings demonstrate that endothelial EP4 is essential for BP homeostasis.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.138505","type":"journal-article","created":{"date-parts":[[2020,7,8]],"date-time":"2020-07-08T11:01:18Z","timestamp":1594206078000},"source":"Crossref","is-referenced-by-count":38,"title":["Endothelial cell prostaglandin E2 receptor EP4 is essential for blood pressure homeostasis"],"prefix":"10.1172","volume":"5","author":[{"given":"Hu","family":"Xu","sequence":"first","affiliation":[{"name":"Advanced Institute for Medical Sciences and"},{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Dalian Medical University, Dalian, China."},{"name":"Liaoning Engineering and Technology Research Center of Nuclear Receptors and Major Metabolic Diseases, Dalian, 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