{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T22:34:10Z","timestamp":1772490850170,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,2,17]],"date-time":"2016-02-17T00:00:00Z","timestamp":1455667200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>In the RELAX\u2010AHF trial, a 48 h i.v. serelaxin infusion reduced systemic vascular resistance in patients with acute heart failure. Consistent with preclinical studies, serelaxin augments endothelial vasodilator function in rat mesenteric arteries. Little is known about the contribution of endothelium\u2010derived relaxing factors after a longer duration of continuous serelaxin treatment. Here we have assessed vascular reactivity and mechanistic pathways in mesenteric arteries and veins and the aorta after 48 or 72 h continuous i.v. infusion of serelaxin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Male rats were infused with either placebo or serelaxin (13.3 \u03bcg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7h<jats:sup>\u22121<\/jats:sup>) via the jugular vein using osmotic minipumps. Vascular function was assessed using wire myography. Changes in gene and protein expression and 6\u2010keto PGF<jats:sub>1\u03b1<\/jats:sub> levels were determined by quantitative PCR, <jats:styled-content style=\"fixed-case\">Western blot<\/jats:styled-content> and ELISA respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Continuous i.v. serelaxin infusion augmented endothelium\u2010dependent relaxation in arteries (mesenteric and aorta) but not in mesenteric veins. In mesenteric arteries, 48 h i.v. serelaxin infusion increased basal NOS activity, associated with increased endothelial NOS (eNOS) expression. Interestingly, phosphorylated\u2010eNOS<jats:sup>Ser1177<\/jats:sup>, eNOS and basal NOS activity were reduced in mesenteric arteries following 72 h serelaxin treatment. At 72 h, serelaxin treatment improved bradykinin\u2010mediated relaxation through COX2\u2010derived PGI<jats:sub>2<\/jats:sub> production.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Continuous i.v. serelaxin infusion enhanced endothelial vasodilator function in arteries but not in veins. The underlying mediator at 48 h was NO but there was a transition to PGI<jats:sub>2<\/jats:sub> by 72 h. Activation of the PGI<jats:sub>2<\/jats:sub>\u2010dependent pathway is key to the prolonged vascular response to serelaxin treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13404","type":"journal-article","created":{"date-parts":[[2015,12,10]],"date-time":"2015-12-10T07:34:21Z","timestamp":1449732861000},"page":"1005-1017","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Time\u2010dependent activation of prostacyclin and nitric oxide pathways during continuous i.v. infusion of serelaxin (recombinant human H2 relaxin)"],"prefix":"10.1111","volume":"173","author":[{"given":"C H","family":"Leo","sequence":"first","affiliation":[{"name":"School of BioSciences The University of Melbourne  Parkville Vic Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Jelinic","sequence":"additional","affiliation":[{"name":"School of BioSciences The University of Melbourne  Parkville Vic 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