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dc.contributor.authorSkeffington, Katie Len
dc.contributor.authorBeck, Christianen
dc.contributor.authorItani, Nozomien
dc.contributor.authorNiu, Youguoen
dc.contributor.authorShaw, Caroline Jen
dc.contributor.authorGiussani, Dinoen
dc.date.accessioned2020-05-11T23:31:58Z
dc.date.available2020-05-11T23:31:58Z
dc.date.issued2020-08en
dc.identifier.issn0194-911X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/305262
dc.description.abstractIn mammals, pregnancy complicated by chronic hypoxia can program hypertension in the adult offspring. However, mechanisms remain uncertain because the partial contributions of the challenge on the placenta, mother and fetus are difficult to disentangle. Here, we used chronic hypoxia in the chicken embryo, an established model system that permits isolation of the direct effects of developmental hypoxia on the cardiovascular system of the offspring, independent of additional effects on the mother and/or the placenta. Fertilised chicken eggs were exposed to normoxia (N; 21% O2) or hypoxia (H; 13.5-14% O2) from the start of incubation (day 0) until day 19 (hatching ~ day 21). Following hatching, all birds were maintained under normoxic conditions until ca. 6 months of adulthood. Hypoxic incubation increased hematocrit (+27%) in the chicken embryo and induced asymmetric growth restriction (body weight –8.6%; biparietal diameter to body weight ratio +7.5%) in the hatchlings (all P<0.05). At adulthood (181 ± 4 days), chickens from hypoxic incubations remained smaller (body weight –7.5%), and showed reduced basal and stimulated in vivo NO bioavailability (pressor response to L-NAME –43%; PE pressor response during NO blockade, –61%) with significant hypertension (MAP +18%), increased cardiac work (ejection fraction +12%; fractional shortening +25%; enhanced baroreflex gain +456%) and left ventricular (LV) wall thickening (LV wall volume +36%; all P<0.05). Therefore, we show that chronic hypoxia can act directly on a developing embryo to program hypertension, cardiovascular dysfunction and cardiac wall remodelling in adulthood in the absence of any maternal or placental effects.
dc.description.sponsorshipThe British Heart Foundation The Wellcome Trust
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.publisherWolters Kluwer Health
dc.rightsAttribution 4.0 International (CC BY)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectCardiovascular Systemen
dc.subjectHearten
dc.subjectAnimalsen
dc.subjectChickensen
dc.subjectHypertensionen
dc.subjectOxidative Stressen
dc.subjectPregnancyen
dc.subjectFemaleen
dc.subjectHypoxiaen
dc.titleHypertension Programmed in Adult Hens by Isolated Effects of Developmental Hypoxia In Ovo.en
dc.typeArticle
prism.endingPage544
prism.issueIdentifier2en
prism.publicationDate2020en
prism.publicationNameHypertension (Dallas, Tex. : 1979)en
prism.startingPage533
prism.volume76en
dc.identifier.doi10.17863/CAM.52348
dcterms.dateAccepted2020-05-08en
rioxxterms.versionofrecord10.1161/hypertensionaha.120.15045en
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2020-08en
dc.contributor.orcidSkeffington, Katie L [0000-0001-5252-6459]
dc.contributor.orcidGiussani, Dino [0000-0002-1308-1204]
dc.identifier.eissn1524-4563
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idBritish Heart Foundation (PG/10/99/28656)
pubs.funder-project-idBritish Heart Foundation (RG/11/16/29260)
pubs.funder-project-idBRITISH HEART FDN (FS/05/111/19956)
cam.orpheus.successMon Jun 22 08:17:28 BST 2020 - Embargo updated*
cam.orpheus.counter6*
rioxxterms.freetoread.startdate2100-01-01


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