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|Title:||Restriction of placental growth results in greater hypotensive response to ?- adrenergic blockade in fetal sheep during late gestation|
|Citation:||Journal of Physiology-London, 2005; 563(2):611-620|
|Publisher:||Blackwell Publishing Ltd|
|Abstract:||Placental 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.|
|Keywords:||Placenta; Animals; Sheep; Placental Insufficiency; Phenylephrine; Phentolamine; Adrenergic alpha-Agonists; Adrenergic alpha-Antagonists; Pregnancy; Blood Pressure; Time Factors; Female; Fetal Hypoxia|
|Appears in Collections:||Molecular and Biomedical Science publications|
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