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dc.contributor.authorNiu, Youguoen
dc.contributor.authorKane, Andrew Den
dc.contributor.authorLusby, Ciara Men
dc.contributor.authorAllison, Beth Jen
dc.contributor.authorChua, Yi Yien
dc.contributor.authorKaandorp, Joepe Jen
dc.contributor.authorNevin-Dolan, Rhiannonen
dc.contributor.authorAshmore, Thomas Jen
dc.contributor.authorBlackmore, Heather Len
dc.contributor.authorDerks, Jan Ben
dc.contributor.authorOzanne, Susanen
dc.contributor.authorGiussani, Dinoen
dc.date.accessioned2018-09-05T12:51:12Z
dc.date.available2018-09-05T12:51:12Z
dc.date.issued2018-10en
dc.identifier.issn0194-911X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/279642
dc.description.abstractIntegrating functional and molecular levels we investigated the effects of maternal treatment with a xanthine oxidase inhibitor on the programming of cardiac dysfunction in adult offspring using an established rat model of hypoxic pregnancy. Female Wistar rats were divided into normoxic or hypoxic (13% O2) pregnancy + maternal Allopurinol treatment (30 mg.Kg-1.d-1). At 4 months, hearts were isolated from 1 male per litter per outcome variable to determine cardiac function and responses to ischaemia-reperfusion (IR) in a Langendorff preparation. Sympathetic dominance, perfusate creatine kinase (CK) and lactate dehydrogenase (LDH) and the cardiac protein expression of the 1 adrenergic receptor, the muscarinic type-2 acetylcholine receptor and the sarcoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) were determined. Relative to controls, offspring from hypoxic pregnancy showed elevated left ventricular end diastolic pressure (+34.7 %), enhanced contractility (dP/dtmax, +41.6 %), reduced coronary flow rate (-21 %) and an impaired recovery to IR (left ventricular diastolic pressure, LVDP, AUC recovery -19.1 %; all P<0.05). Increased sympathetic reactivity (heart rate, +755.5 %, LVDP, +418.9 %) contributed to the enhanced myocardial contractility (P<0.05). Perfusate CK (+431 %) and LDH (+251.3 %) and the cardiac expression of SERCA2a (+71.4 %) were also elevated (P<0.05), further linking molecular markers of cardiac stress and injury to dysfunction. Maternal Allopurinol restored all functional and molecular indices of cardiac pathology. The data support a link between xanthine oxidase-derived oxidative stress in hypoxic pregnancy and cardiac dysfunction in the adult offspring, providing a target for early intervention in the developmental programming of heart disease.
dc.description.sponsorshipBritish Heart Foundation
dc.format.mediumPrinten
dc.languageengen
dc.publisherWolters Kluwer Health
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectSympathetic Nervous Systemen
dc.subjectAnimalsen
dc.subjectRatsen
dc.subjectPregnancy Complicationsen
dc.subjectAllopurinolen
dc.subjectXanthine Oxidaseen
dc.subjectReceptors, Adrenergic, betaen
dc.subjectReceptor, Muscarinic M2en
dc.subjectEnzyme Inhibitorsen
dc.subjectHeart Function Testsen
dc.subjectOxidative Stressen
dc.subjectPregnancyen
dc.subjectMyocardial Contractionen
dc.subjectFemaleen
dc.subjectMaleen
dc.subjectSarcoplasmic Reticulum Calcium-Transporting ATPasesen
dc.subjectHeart Failureen
dc.subjectHypoxiaen
dc.titleMaternal Allopurinol Prevents Cardiac Dysfunction in Adult Male Offspring Programmed by Chronic Hypoxia During Pregnancy.en
dc.typeArticle
prism.endingPage978
prism.issueIdentifier4en
prism.publicationDate2018en
prism.publicationNameHypertension (Dallas, Tex. : 1979)en
prism.startingPage971
prism.volume72en
dc.identifier.doi10.17863/CAM.27011
dcterms.dateAccepted2018-08-02en
rioxxterms.versionofrecord10.1161/hypertensionaha.118.11363en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2018-10en
dc.contributor.orcidOzanne, Susan [0000-0001-8753-5144]
dc.contributor.orcidGiussani, Dino [0000-0002-1308-1204]
dc.identifier.eissn1524-4563
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idBritish Heart Foundation (PG/06/060/20918)
pubs.funder-project-idBritish Heart Foundation (RG/06/006/22028)
pubs.funder-project-idBritish Heart Foundation (RG/11/16/29260)
pubs.funder-project-idIsaac Newton Trust (MINUTE 544(I))
pubs.funder-project-idLister Institute of Preventive Medicine (unknown)
pubs.funder-project-idWellcome Trust (072256/Z/03/Z)
pubs.funder-project-idSir Jules Thorn Charitable Trust (05SC/06A)
pubs.funder-project-idBBSRC (BB/E002668/1)
pubs.funder-project-idBRITISH HEART FDN (FS/05/111/19956)
pubs.funder-project-idRoyal Society (wm062239)
pubs.funder-project-idBritish Heart Foundation (FS/12/74/29778)
pubs.funder-project-idBritish Heart Foundation (PG/14/5/30547)
pubs.funder-project-idWellcome Trust (072256/Z/03/A)
pubs.funder-project-idWellcome Trust (089941/Z/09/A)
pubs.funder-project-idLister Institute of Preventive Medicine (unknown)
pubs.funder-project-idBritish Heart Foundation (RG/17/8/32924)
pubs.funder-project-idBritish Heart Foundation (FS/09/029/27902)
pubs.funder-project-idMRC (MC_UU_12012/4)
cam.orpheus.successThu Jan 30 10:54:40 GMT 2020 - The item has an open VoR version.*
rioxxterms.freetoread.startdate2100-01-01


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International