{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T06:41:04Z","timestamp":1769150464210,"version":"3.49.0"},"reference-count":61,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,10,31]],"date-time":"2019-10-31T00:00:00Z","timestamp":1572480000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1059960"],"award-info":[{"award-number":["1059960"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Endothelium\u2010derived vasoconstriction is a hallmark of vascular dysfunction in hypertension. In some cases, an overproduction of endothelium\u2010derived prostacyclin (PGI<jats:sub>2<\/jats:sub>) can cause contraction rather than relaxation. Relaxin is well known for its vasoprotective actions, but the possibility that this peptide could also reverse endothelium\u2010derived vasoconstriction has never been investigated. We tested the hypothesis that short\u2010term relaxin treatment mitigates endothelium\u2010derived vasoconstriction in spontaneously hypertensive rats (SHR).<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Male Wistar Kyoto rats (WKY) and SHR were subcutaneously infused with either vehicle (20\u00a0mmol\u00b7L<jats:sup>\u22121<\/jats:sup> sodium acetate) or relaxin (13.3\u00a0\u03bcg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7hr<jats:sup>\u22121<\/jats:sup>) using osmotic minipumps for 3\u00a0days. Vascular reactivity to the endothelium\u2010dependent agonist ACh was assessed in vitro by wire myography. Quantitative PCR and LC\u2010MS were used to identify changes in gene expression of prostanoid pathways and PG production, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Relaxin treatment ameliorated hypertension\u2010induced endothelial dysfunction by increasing NO\u2010dependent relaxation and reducing endothelium\u2010dependent contraction. Notably, short\u2010term relaxin treatment up\u2010regulated mesenteric PGI<jats:sub>2<\/jats:sub> receptor (IP) expression, permitting PGI<jats:sub>2<\/jats:sub>\u2013IP\u2010mediated vasorelaxation. In the aorta, reversal of contraction was accompanied by suppression of the hypertension\u2010induced increase in prostanoid\u2010producing enzymes and reduction in PGI<jats:sub>2<\/jats:sub>\u2010evoked contractions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Relaxin has region\u2010dependent vasoprotective actions in hypertension. Specifically, relaxin has distinct effects on endothelium\u2010derived contracting factors and their associated vasoconstrictor pathways in mesenteric arteries and the aorta. Taken together, these observations reveal the potential of relaxin as a new therapeutic agent for vascular disorders that are associated with endothelium\u2010derived vasoconstriction including hypertension.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14858","type":"journal-article","created":{"date-parts":[[2019,9,3]],"date-time":"2019-09-03T18:43:13Z","timestamp":1567536193000},"page":"217-233","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Relaxin reduces endothelium\u2010derived vasoconstriction in hypertension: Revealing new therapeutic insights"],"prefix":"10.1111","volume":"177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1424-9694","authenticated-orcid":false,"given":"Chen Huei","family":"Leo","sequence":"first","affiliation":[{"name":"School of Biosciences The University of Melbourne  Parkville VIC 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