Increased fetal blood pressure response to maternal norepinephrine after pharmacological inhibition f norepinephrine uptake in pregnant sheep

Abstract

Norepinephrine (NE) is elevated in pregnancies complicated by preeclampsia (PE). Specific uptake of NE by the NE transporter (NET) plays a central role as regulator of NE levels. Expression of NET is reduced in placentas from PE pregnancies. To study adverse fetal effects of reduced NET expression on the placental buffering capacity, the NET was pharmacologically blocked by a specific uptake inhibitor reboxetine. We evaluated the effect of NE uptake inhibition on maternal and fetal arterial blood pressure responses to increasing maternal doses of NE in 10 chronically prepared fetal sheep. Arterial blood pressure was monitored continuously during increasing doses of i.v. NE. NET inhibition increased both fetal and maternal mean arterial blood pressure (p < 0.001, respectively). Reuptake by NET appears to be a mechanism protecting the fetus from NE. A reduced uptake capacity in preeclamptic pregnancies due to reduced NE uptake may lead to increased fetal arterial blood pressure.