Restriction of placental growth results in greater hypotensive response to ?- adrenergic blockade in fetal sheep during late gestation

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dc.contributor.authorDanielson, L.
dc.contributor.authorMcMillen, I.
dc.contributor.authorWright, J.
dc.contributor.authorMorrison, J.
dc.date.issued2005
dc.description.abstractPlacental insufficiency resulting in restriction of fetal substrate supply and fetal hypoxaemia is a major cause of restricted fetal growth and increased neonatal morbidity. Fetal adaptations to placental restriction (PR) include increases in circulating catecholamines and cortisol and decreased fetal body growth, with relative sparing of brain growth. The mechanisms underlying the redistribution of fetal cardiac output in PR fetuses are not known and the aim of this study was to determine whether maintenance of fetal blood pressure (BP) in the PR fetus is dependent on alpha-adrenergic stimulation. PR was induced by removing the majority of uterine caruncles in the ewe before conception. Sterile vascular surgery was performed on seven PR and six control fetuses at 113-120 days' gestation (term = 150 +/- 3 days). Fetuses with a mean arterial PO2 < 17 mmHg between 123 and 127 days' gestation were defined as hypoxic. There was a greater fall (P < 0.05) in fetal BP during phentolamine infusion (i.v: 5 mg bolus, 0.2 mg kg(-1) min(-1) for 2 h) in the hypoxic PR group (-15 +/- 2 mmHg) compared with normoxic controls (-5 +/- 1 mmHg). The fall in fetal BP during phentolamine infusion was directly related to the level of fetal PO2. Fetal BP and HR responses to phenylephrine (i.v.: 40 microg kg(-1)) were not different between PR and control fetuses. The maintenance of BP in the chronically hypoxic fetus is therefore dependent on alpha-adrenergic activation, and this fetal adaptation to a suboptimal intrauterine environment pre-dates the development of significant growth restriction. While this adaptation may play a critical role in the redistribution of fetal cardiac output to ensure the sparing of brain growth, it may have adverse consequences for peripheral vascular function in the neonatal period and in adult life.
dc.identifier.citationJournal of Physiology, 2005; 563(2):611-620
dc.identifier.doi10.1113/jphysiol.2004.080523
dc.identifier.issn0022-3751
dc.identifier.issn1469-7793
dc.identifier.urihttp://hdl.handle.net/2440/27594
dc.language.isoen
dc.publisherBlackwell Publishing Ltd
dc.source.urihttps://doi.org/10.1113/jphysiol.2004.080523
dc.subjectAnimals
dc.subjectSheep
dc.subjectPlacental Insufficiency
dc.subjectPhenylephrine
dc.subjectPhentolamine
dc.subjectAdrenergic alpha-Agonists
dc.subjectAdrenergic alpha-Antagonists
dc.subjectPregnancy
dc.subjectPlacentation
dc.subjectBlood Pressure
dc.subjectTime Factors
dc.subjectFemale
dc.subjectFetal Hypoxia
dc.titleRestriction of placental growth results in greater hypotensive response to ?- adrenergic blockade in fetal sheep during late gestation
dc.typeJournal article
pubs.publication-statusPublished

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