PLACENTAL NOREPINEPHRINE CLEARANCE - IN-VIVO MEASUREMENT AND PHYSIOLOGICAL-ROLE

The intrauterine clearance rate of catecholamines is higher than in ne wborn animals or in adults. The separate contributions of the fetus an d placenta to this clearance are not known. The placenta is a site of expression of the amine plasma membrane transporters that mediate this process. To determine the physiological role of this placental transp orter in vivo, we studied fetal sheep at 123 days with common umbilica l vein (UV), fetal arterial (AO), and venous catheters. Tritiated nore pinephrine ([H-3]NE) was infused to determine the kinetics of placenta l and fetal NE appearance and clearance rates. Umbilical flow was dete rmined by [H-3]NE infusion. Placental and total (fetal-placental) NE c learance rates were determined by measurement of [H-3]NE from simultan eously drawn UV and AO samples. Total clearance was 99 +/- 8 ml . kg(- 1). min(-1). Placental fractional [H-3]NE extraction was 21% and accou nted for 48% of total clearance. Fetal plasma NE production rate was 8 5 +/- 20 ng . kg(-1). min(-1). We conclude that placental catecholamin e clearance is an important metabolic function of the placenta. This m echanism for clearance of the high fetal production rate of catecholam ines is vital for fetal homeostasis. We speculate that derangements in placental catecholamine clearance may explain the exaggerated adverse effects on the fetus of drugs like cocaine, which block catecholamine transport.