Chronic Norepinephrine Exposure and Whole Blood Detection in Fetal Sheep

Abstract

Placenta insufficiency results in decreased nutrient supply between the mother and fetus, which induces hypoxemia and hypoglycemia in the fetuses causing intrauterine growth restriction. The fetus increases circulating norepinephrine concentrations in response to this stress, which can cause adrenergic receptor desensitization. The aim of this study was to determine what adrenergic receptors were detectable in fetal whole blood mRNA and to determine whether tissue desensitization manifested in the form of low adrenergic receptor mRNA concentrations. Three of the nine adrenergic receptor subtypes (α2A, β1 and β2) were detectable in RNA extracted from fetal whole blood of control and placenta insufficient treatment groups. Of these three, adrenergic receptor α2A was expressed in the greatest concentration and was chosen for further study. In placenta insufficient fetuses adrenergic receptor α2A mRNA concentrations were 73% lower than the control group. We also measured adrenergic receptor α2A mRNA in fetuses without an adrenal medulla, which were not responsive to hypoxemia-induced elevation of norepinephrine. These placental insufficient fetuses were no different from the controls and therefore, the evidence supports the increase of norepinephrine, rather than the hypoxic conditions, as the cause of desensitization in whole blood samples.