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Does prenatal hypoxia lead to permanent cardiovascular change in the offspring?
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. University of Sydney.
2015 (English)Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

Chronic prenatal hypoxia is associated with intrauterine growth retardation and there is now some evidence that it also induces programmed hypertension in offspring. However these studies are generally confounded as hypoxia is either induced by maternal hypoxia or placental insufficiency. The study described in this thesis is designed to overcome this problem. Pregnant rats were dosed daily with the drug dofetilide (2.5 mg/kg) or water on GD 11-14 and the cardiovascular parameters of the offspring at 8-12 weeks (>300g) were analysed using implanted telemetry blood pressure (BP) transmitters.Dofetilide is a class III antiarrhythmic drug that selectively blocks the Ikr channel which is expressed in the rat embryo but not in the adult rat. When administered to pregnant rats it induces bradycardia (and associated hypoxia) in the embryos without affecting maternal oxygenation or heart rate. Embryo culture studies showed that dofetilide induced a period of embryonic bradycardia for up to 9 hours following each dose. The dofetilide treated-rats had less completed pregnancies, smaller litters and lower weight pups compared to controls. At 8-12 weeks age the dofetilide offspring has increased BP (+10-12%) compared with controls. Postnatal stress in the form of air puffs did not reveal other cardiovascular differences between control and dofetilide offspring. The increased BP was not associated with an increased HR or changes in the autonomic nervous system. Remaining unexplored possibilities include impaired nephrogenesis, vascular dysfunction and microvascular

Place, publisher, year, edition, pages
2015. , p. 48
Keywords [en]
Developmental programming, hypoxia, dofetilide, telemetry
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:uu:diva-242903OAI: oai:DiVA.org:uu-242903DiVA, id: diva2:785361
Subject / course
Toxicology
Educational program
Master of Science Programme in Pharmacy
Supervisors
Examiners
Available from: 2017-05-11 Created: 2015-02-02 Last updated: 2018-01-11Bibliographically approved

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CiteExportLink to record
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Citation style
  • apa
  • ieee
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