Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/32708
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dc.contributor.authorBrookes, Z. L.-
dc.contributor.authorStedman, E. N.-
dc.contributor.authorBrown, N. J.-
dc.contributor.authorHebbes, Christopher P.-
dc.contributor.authorGuerrini, R.-
dc.contributor.authorCalo, G.-
dc.contributor.authorReilly, C. S.-
dc.contributor.authorLambert, David G.-
dc.date.accessioned2015-07-20T08:33:44Z-
dc.date.available2015-07-20T08:33:44Z-
dc.date.issued2013-09-23-
dc.identifier.citationPLoS One, 2013, 8 (9), e74943en
dc.identifier.urihttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0074943en
dc.identifier.urihttp://hdl.handle.net/2381/32708-
dc.description.abstractMicrovascular inflammation occurs during sepsis and the endogenous opioid-like peptide nociceptin/orphanin FQ (N/OFQ) is known to regulate inflammation. This study aimed to determine the inflammatory role of N/OFQ and its receptor NOP (ORL1) within the microcirculation, along with anti-inflammatory effects of the NOP antagonist UFP-101 (University of Ferrara Peptide-101) in an animal model of sepsis (endotoxemia). Male Wistar rats (220 to 300 g) were administered lipopolysaccharide (LPS) for 24 h (-24 h, 1 mg kg(-1); -2 h, 1 mg kg(-1) i.v., tail vein). They were then either anesthetised for observation of the mesenteric microcirculation using fluorescent in vivo microscopy, or isolated arterioles (~200 µm) were studied in vitro with pressure myography. 200 nM kg(-1) fluorescently labelled N/OFQ (FITC-N/OFQ, i.a., mesenteric artery) bound to specific sites on the microvascular endothelium in vivo, indicating sparse distribution of NOP receptors. In vitro, arterioles (~200 µm) dilated to intraluminal N/OFQ (10(-5)M) (32.6 + 8.4%) and this response was exaggerated with LPS (62.0 +7.9%, p=0.031). In vivo, LPS induced macromolecular leak of FITC-BSA (0.02 g kg(-1) i.v.) (LPS: 95.3 (86.7 to 97.9)%, p=0.043) from post-capillary venules (<40 µm) and increased leukocyte rolling as endotoxemia progressed (p=0.027), both being reduced by 150 nmol kg(-1) UFP-101 (i.v., jugular vein). Firstly, the rat mesenteric microcirculation expresses NOP receptors and secondly, NOP function (ability to induce dilation) is enhanced with LPS. UFP-101 also reduced microvascular inflammation to endotoxemia in vivo. Hence inhibition of the microvascular N/OFQ-NOP pathway may have therapeutic potential during sepsis and warrants further investigation.en
dc.language.isoenen
dc.publisherPublic Library of Scienceen
dc.relation.urihttp://www.ncbi.nlm.nih.gov/pubmed/24086402-
dc.rightsCopyright © 2013 Brookes et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.subjectAnimalsen
dc.subjectCHO Cellsen
dc.subjectCardiovascular Systemen
dc.subjectCricetinaeen
dc.subjectCricetulusen
dc.subjectFluorescein-5-isothiocyanateen
dc.subjectInflammationen
dc.subjectLeukocyte Rollingen
dc.subjectMaleen
dc.subjectMicrocirculationen
dc.subjectMicrovesselsen
dc.subjectNarcotic Antagonistsen
dc.subjectOpioid Peptidesen
dc.subjectRatsen
dc.subjectRats, Wistaren
dc.subjectReceptors, Opioiden
dc.subjectRecombinant Proteinsen
dc.titleThe Nociceptin/Orphanin FQ Receptor Antagonist UFP-101 Reduces Microvascular Inflammation to Lipopolysaccharide In Vivoen
dc.typeJournal Articleen
dc.identifier.doi10.1371/journal.pone.0074943-
dc.identifier.eissn1932-6203-
dc.identifier.piiPONE-D-13-19778-
dc.description.statusPeer-revieweden
dc.description.versionPublisher Versionen
dc.type.subtypeJournal Article-
pubs.organisational-group/Organisationen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGYen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicineen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Cardiovascular Sciencesen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/Themesen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/Themes/Cardiovascularen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/Themes/Molecular & Cellular Bioscienceen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/Themes/Neuroscience & Behaviouren
dc.dateaccepted2013-08-07-
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

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