{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T16:08:03Z","timestamp":1785946083571,"version":"3.56.0"},"reference-count":59,"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 Endothelial NO synthase plays a central role in regulating vasodilation and blood pressure. Intracellular Ca\n 2+<\/jats:sup>\n mobilization is a critical modulator of endothelial NO synthase function, and increased cytosolic Ca\n 2+<\/jats:sup>\n concentration in endothelial cells is able to induce endothelial NO synthase phosphorylation. Ca\n 2+<\/jats:sup>\n release mediated by 3 subtypes of inositol 1,4,5\u2010trisphosphate receptors (\n IP<\/jats:styled-content>\n 3<\/jats:sub>\n Rs) from the endoplasmic reticulum and subsequent Ca\n 2+<\/jats:sup>\n entry after endoplasmic reticulum Ca\n 2+<\/jats:sup>\n store depletion has been proposed to be the major pathway to mobilize Ca\n 2+<\/jats:sup>\n in endothelial cells. However, the physiological role of\n IP<\/jats:styled-content>\n 3<\/jats:sub>\n Rs in regulating blood pressure remains largely unclear.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n To investigate the role of endothelial\n IP<\/jats:styled-content>\n 3<\/jats:sub>\n Rs in blood pressure regulation, we first generated an inducible endothelial cell\u2013specific\n IP<\/jats:styled-content>\n 3<\/jats:sub>\n R1 knockout mouse model and found that deletion of\n IP<\/jats:styled-content>\n 3<\/jats:sub>\n R1 in adult endothelial cells did not affect vasodilation and blood pressure. Considering all 3 subtypes of\n IP<\/jats:styled-content>\n 3<\/jats:sub>\n Rs are expressed in mouse endothelial cells, we further generated inducible endothelial cell\u2013specific\n IP<\/jats:styled-content>\n 3<\/jats:sub>\n R triple knockout mice and found that deletion of all 3\n IP<\/jats:styled-content>\n 3<\/jats:sub>\n R subtypes decreased plasma\n NO<\/jats:styled-content>\n concentration and increased basal blood pressure. Furthermore,\n IP<\/jats:styled-content>\n 3<\/jats:sub>\n R deficiency reduced acetylcholine\u2010induced vasodilation and endothelial NO synthase phosphorylation at Ser1177.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Our results reveal that\n IP<\/jats:styled-content>\n 3<\/jats:sub>\n R\u2010mediated Ca\n 2+<\/jats:sup>\n release in vascular endothelial cells plays an important role in regulating vasodilation and physiological blood pressure.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.118.011704","type":"journal-article","created":{"date-parts":[[2019,2,13]],"date-time":"2019-02-13T10:02:27Z","timestamp":1550052147000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":37,"title":["Inositol 1,4,5\u2010Trisphosphate Receptors in Endothelial Cells Play an Essential Role in Vasodilation and Blood Pressure Regulation"],"prefix":"10.1161","volume":"8","author":[{"given":"Qingsong","family":"Lin","sequence":"first","affiliation":[{"name":"Drug Discovery Center State Key Laboratory of Chemical Oncogenomics School of Chemical Biology and Biotechnology Peking University Shenzhen Graduate School Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Drug Discovery Center State Key Laboratory of Chemical Oncogenomics School of Chemical Biology and Biotechnology Peking University Shenzhen Graduate School Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Jing","sequence":"additional","affiliation":[{"name":"Department of Cardiology The Second Xiangya Hospital Central South University Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christa","family":"Trexler","sequence":"additional","affiliation":[{"name":"Department of 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