{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:34:44Z","timestamp":1771461284695,"version":"3.50.1"},"reference-count":67,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2019,2,19]]},"abstract":"\n Background<\/jats:title>\n \n Prostaglandin E\n 2<\/jats:sub>\n (\n PGE<\/jats:styled-content>\n 2<\/jats:sub>\n ) is a major prostanoid with multiple actions that potentially affect blood pressure (\n BP<\/jats:styled-content>\n ).\n PGE<\/jats:styled-content>\n 2<\/jats:sub>\n acts through 4 distinct E\u2010prostanoid (\n EP<\/jats:styled-content>\n ) receptor isoforms:\n EP<\/jats:styled-content>\n 1 to\n EP<\/jats:styled-content>\n 4. The\n EP<\/jats:styled-content>\n 4 receptor (\n EP<\/jats:styled-content>\n 4R) promotes\n PGE<\/jats:styled-content>\n 2<\/jats:sub>\n \u2010dependent vasodilation, but its role in the pathogenesis of hypertension is not clear.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n To address this issue, we studied mice after temporal\u2010 and cell\u2010specific deletion of\n EP<\/jats:styled-content>\n 4R. First, using a mouse line with loss of\n EP<\/jats:styled-content>\n 4 expression induced universally after birth, we confirm that\n EP<\/jats:styled-content>\n 4R mediates a major portion of the acute vasodilatory effects of infused\n PGE<\/jats:styled-content>\n 2<\/jats:sub>\n . In addition,\n EP<\/jats:styled-content>\n 4 contributes to control of resting\n BP<\/jats:styled-content>\n , which was increased by 5\u00b11\u00a0mm\u00a0Hg in animals with generalized deficiency of this receptor. We also show that\n EP<\/jats:styled-content>\n 4 is critical for limiting elevations in\n BP<\/jats:styled-content>\n caused by high salt feeding and long\u2010term infusion of angiotensin\n II<\/jats:styled-content>\n . To more precisely identify the mechanism for these actions, we generated mice in which\n EP<\/jats:styled-content>\n 4R loss is induced after birth and is limited to smooth muscle. In these mice, acute\n PGE<\/jats:styled-content>\n 2<\/jats:sub>\n \u2010dependent vasodilation was attenuated, indicating that this response is mediated by\n EP<\/jats:styled-content>\n 4R in vascular smooth muscle cells. However, absence of\n EP<\/jats:styled-content>\n 4R only in this vascular compartment had a paradoxical effect of lowering resting\n BP<\/jats:styled-content>\n , whereas the protective effect of\n EP<\/jats:styled-content>\n 4R on limiting angiotensin II\u2013dependent hypertension was unaffected.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Taken together, our findings support a complex role for\n EP<\/jats:styled-content>\n 4R in regulation of\n BP<\/jats:styled-content>\n and in hypertension, which appears to involve actions of the\n EP<\/jats:styled-content>\n 4R in tissues beyond vascular smooth muscle cells.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.118.010745","type":"journal-article","created":{"date-parts":[[2019,2,15]],"date-time":"2019-02-15T10:00:44Z","timestamp":1550224844000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":10,"title":["Complex Role for E\u2010Prostanoid 4 Receptors in Hypertension"],"prefix":"10.1161","volume":"8","author":[{"given":"Marcela","family":"Herrera","sequence":"first","affiliation":[{"name":"Division of Nephrology Department of Medicine Duke University Durham NC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Nephrology Department of Medicine Duke University Durham NC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew A.","family":"Sparks","sequence":"additional","affiliation":[{"name":"Division of Nephrology Department of Medicine Duke University Durham NC"},{"name":"Renal Section Durham VA Medical Center Durham NC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael W.","family":"Manning","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Duke University Durham NC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beverly H.","family":"Koller","sequence":"additional","affiliation":[{"name":"Department of Genetics University of North Carolina Chapel Hill NC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas M.","family":"Coffman","sequence":"additional","affiliation":[{"name":"Division of Nephrology Department of Medicine Duke University Durham NC"},{"name":"Renal Section Durham VA Medical Center Durham NC"},{"name":"Cardiovascular and Metabolic Disorders Research Program Duke\u2013National University of Singapore Graduate Medical School Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200113455"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.1.2.3111928"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000136134.31846.83"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000035856.77718.DA"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000127578.21885.3E"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003787"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.4.6.809"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jhh.1000981"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-6386(85)80063-9"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.112.110726"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2010.09.004"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.86.6.663"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.30.3.664"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-05-155408"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20082293"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200838969"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2541"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2015.169"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2014.173"},{"key":"e_1_3_1_21_2","first-page":"205","article-title":"International union of pharmacology classification of prostanoid receptors: properties, distribution, and structure of the receptors and their subtypes","volume":"46","author":"Coleman RA","year":"1994","unstructured":"Coleman RA, Smith WL, Narumiya S. 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