Endothelin and the regulation of uterine and placental perfusion in hypoxia-induced fetal growth restriction
- PMID: 14706678
- DOI: 10.1016/j.jsgi.2003.07.001
Endothelin and the regulation of uterine and placental perfusion in hypoxia-induced fetal growth restriction
Abstract
Objective: Normal placental function is dependent on maintenance of uteroplacental perfusion. Endothelin, a potent vasoconstrictor, is produced in and is active in the uteroplacental vasculature. The purpose of this study was to determine the role of endothelin in the regulation of uteroplacental perfusion under normal conditions, and in hypoxia-induced fetal growth restriction.
Methods: Timed-pregnant Sprague-Dawley rats, outfitted with arterial catheters, were maintained in either a normoxic or a normobaric hypoxic (12% oxygen) atmosphere from day 18 to 21 of gestation. During this time, the endothelin receptor A antagonist, A-127722, or its vehicle was administered. Regional blood flow was determined on gestational day 21 using 57Co-labeled microspheres. Data were analyzed by analysis of variance with statistical significance accepted at P<.05.
Results: Both placental and uterine placental bed perfusion were significantly decreased by hypoxia and returned to normal values with the endothelin antagonist (P<.01 and P<.05, respectively). Fetal weights were significantly lower in the hypoxic group (P<.001) and restored to control levels by the antagonist.
Conclusion: In the rat, endothelin contributes little to the regulation of uteroplacental perfusion under normal conditions. Hypoxia results in a decrease in perfusion of the uteroplacental bed and of the placenta, and perfusion in both of these beds is normalized by endothelin A receptor antagonism. We conclude that endothelin plays a primary role in the pathophysiology of hypoxia-induced fetal growth restriction by reducing uteroplacental perfusion.
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