Endothelin and platelet-activating factor: Significance in the pathophysiology of ischemia/reperfusion-induced fetal growth restriction in the rat

    loading  Checking for direct PDF access through Ovid

Abstract

Objective

The objective of the study was to evaluate the role of endothelin-1 and platelet-activating factor in ischemia/reperfusion-induced fetal growth restriction in the rat.

Study design

On day 17 of gestation, the right uterine and ovarian arteries were occluded for 30 minutes in experimental but not sham-operated rats. All rats received endothelin receptor A antagonist, A-127722 (10 mg/kg per day), platelet-activating factor antagonist, WEB-2086 (1 mg/kg), or vehicle. On gestational day 21, litter size, fetal viability, and fetal and placental weights were recorded. Reverse transcription–polymerase chain reaction for phospholipase A2-IIA and preproendothelin-1 messenger ribonucleic acid was performed on uterus and placentas from each uterine horn. Groups were compared statistically by analysis of variance.

Results

Ischemia/reperfusion reduced fetal weights, in both the ischemic horn and the nonischemic horn (P < .001). Antagonism of either endothelin receptor A or platelet-activating factor normalized fetal growth in both horns. Neither placental weight nor the incidence of fetal demise was affected by ischemia/reperfusion. Phospholipase A2-IIA and preproendothelin-1 messenger ribonucleic acid expression did not differ between right and left uterine horns in any group. Uterine and placental tissues in the ischemia/reperfusion group exhibited increased phospholipase A2-IIA (P < .01) but not preproendothelin-1.

Conclusion

Endothelin-1 and platelet-activating factor are both important mediators in the pathophysiology of ischemia/reperfusion-induced fetal growth restriction in the rat, contributing to the fetal growth restriction observed in both the ischemic and nonischemic horns. Antagonism of either mediator produces normal fetal growth in this model of fetal growth restriction.

Related Topics

    loading  Loading Related Articles