{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T17:34:39Z","timestamp":1782840879751,"version":"3.54.5"},"reference-count":55,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T00:00:00Z","timestamp":1658707200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"RANZCOG Women\u2019s Health Foundation Arthur Wilson Memorial Scholarship","award":["1159261"],"award-info":[{"award-number":["1159261"]}]},{"name":"RANZCOG Women\u2019s Health Foundation Arthur Wilson Memorial Scholarship","award":["1146128"],"award-info":[{"award-number":["1146128"]}]},{"name":"RANZCOG Women\u2019s Health Foundation Arthur Wilson Memorial Scholarship","award":["1150828"],"award-info":[{"award-number":["1150828"]}]},{"name":"N.P. National Health and Medical Research Council","award":["1159261"],"award-info":[{"award-number":["1159261"]}]},{"name":"N.P. National Health and Medical Research Council","award":["1146128"],"award-info":[{"award-number":["1146128"]}]},{"name":"N.P. National Health and Medical Research Council","award":["1150828"],"award-info":[{"award-number":["1150828"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Preeclampsia is a devastating, multisystem disorder of pregnancy. It has no cure except delivery, which if premature can impart significant neonatal morbidity. Efforts to repurpose pregnancy-safe therapeutics for the treatment of preeclampsia have led to the assessment of the proton pump inhibitor, esomeprazole. Preclinically, esomeprazole reduced placental secretion of anti-angiogenic sFlt-1, improved endothelial dysfunction, promoted vasorelaxation, and reduced maternal hypertension in a mouse model. Our understanding of the precise mechanisms through which esomeprazole works to reduce endothelial dysfunction and enhance vasoreactivity is limited. Evidence from earlier studies suggested esomeprazole might work via the nitric oxide pathway, upregulating endothelial nitric oxide synthase (eNOS). Here, we investigated the effect of esomeprazole in a mouse model of L-NAME-induced hypertension (decreased eNOS activity). We further antagonised the model by addition of diet-induced obesity, which is relevant to both preeclampsia and the nitric oxide pathway. Esomeprazole did not decrease blood pressure in this model, nor were there any alterations in vasoreactivity or changes in foetal outcomes in lean mice. We observed similar findings in the obese mouse cohort, except esomeprazole treatment enhanced ex vivo acetylcholine-induced vasorelaxation. As acetylcholine induces nitric oxide production, these findings hint at a function for esomeprazole in the nitric oxide pathway.<\/jats:p>","DOI":"10.3390\/ijms23158185","type":"journal-article","created":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T21:20:59Z","timestamp":1658784059000},"page":"8185","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Actions of Esomeprazole on the Maternal Vasculature in Lean and Obese Pregnant Mice with Impaired Nitric Oxide Synthesis: A Model of Preeclampsia"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8376-0096","authenticated-orcid":false,"given":"Natasha","family":"de Alwis","sequence":"first","affiliation":[{"name":"Therapeutics Discovery & Vascular Function Group, Department of Obstetrics and Gynaecology, The University of Melbourne, Mercy Hospital for Women, Heidelberg, VIC 3084, Australia"},{"name":"Mercy Perinatal, Mercy Hospital for Women, Heidelberg, VIC 3084, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie K.","family":"Binder","sequence":"additional","affiliation":[{"name":"Therapeutics Discovery & Vascular Function Group, Department of Obstetrics and Gynaecology, The University of Melbourne, Mercy Hospital for Women, Heidelberg, VIC 3084, Australia"},{"name":"Mercy Perinatal, Mercy Hospital for Women, Heidelberg, VIC 3084, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeukai T. M.","family":"Mangwiro","sequence":"additional","affiliation":[{"name":"Therapeutics Discovery & Vascular Function Group, Department of Obstetrics and Gynaecology, The University of Melbourne, Mercy Hospital for Women, Heidelberg, VIC 3084, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally","family":"Beard","sequence":"additional","affiliation":[{"name":"Therapeutics Discovery & Vascular Function Group, Department of Obstetrics and Gynaecology, The University of Melbourne, Mercy Hospital for Women, Heidelberg, VIC 3084, Australia"},{"name":"Mercy Perinatal, Mercy Hospital for Women, Heidelberg, VIC 3084, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha","family":"Pritchard","sequence":"additional","affiliation":[{"name":"Mercy Perinatal, Mercy Hospital for Women, Heidelberg, VIC 3084, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elif","family":"Kadife","sequence":"additional","affiliation":[{"name":"Mercy Perinatal, Mercy Hospital for Women, Heidelberg, VIC 3084, Australia"},{"name":"Obstetrics Diagnostics and Therapeutics Group, Department of Obstetrics and Gynaecology, The University of Melbourne, Mercy Hospital for Women, Heidelberg, VIC 3084, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1908-784X","authenticated-orcid":false,"given":"Bianca R.","family":"Fato","sequence":"additional","affiliation":[{"name":"Therapeutics Discovery & Vascular Function Group, Department of Obstetrics and Gynaecology, The University of Melbourne, Mercy Hospital for Women, Heidelberg, VIC 3084, Australia"},{"name":"Mercy Perinatal, Mercy Hospital for Women, Heidelberg, VIC 3084, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1966-2293","authenticated-orcid":false,"given":"Emerson","family":"Keenan","sequence":"additional","affiliation":[{"name":"Mercy Perinatal, Mercy Hospital for Women, Heidelberg, VIC 3084, Australia"},{"name":"Obstetrics Diagnostics and Therapeutics Group, Department of Obstetrics and Gynaecology, The University of Melbourne, Mercy Hospital for Women, Heidelberg, VIC 3084, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona C.","family":"Brownfoot","sequence":"additional","affiliation":[{"name":"Mercy Perinatal, Mercy Hospital for Women, Heidelberg, VIC 3084, Australia"},{"name":"Obstetrics Diagnostics and Therapeutics Group, Department of Obstetrics and Gynaecology, The University of Melbourne, Mercy Hospital for Women, Heidelberg, VIC 3084, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tu\u2019uhevaha J.","family":"Kaitu\u2019u-Lino","sequence":"additional","affiliation":[{"name":"Mercy Perinatal, Mercy Hospital for Women, Heidelberg, VIC 3084, Australia"},{"name":"Diagnostics Discovery and Reverse Translation in Pregnancy, The University of Melbourne, Mercy Hospital for Women, Heidelberg, VIC 3084, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie J.","family":"Hannan","sequence":"additional","affiliation":[{"name":"Therapeutics Discovery & Vascular Function Group, Department of Obstetrics and Gynaecology, The University of Melbourne, Mercy Hospital for Women, Heidelberg, VIC 3084, Australia"},{"name":"Mercy Perinatal, Mercy Hospital for Women, Heidelberg, VIC 3084, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejogrb.2013.05.005","article-title":"Global and regional estimates of preeclampsia and eclampsia: A systematic review","volume":"170","author":"Abalos","year":"2013","journal-title":"Eur. 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