Endothelin: release by and potent constrictor effect on the fetal vessels of human perfused placental lobules

Abstract

Human placental lobules were bilaterally perfused with a modified Krebs solution at constant flow rates of 5 mL min-1, and fetal inflow perfusion pressure was recorded. The effect of infusions of endothelin-1 and endothelin-3 (ET-1 and ET-3) on the perfusion pressure was assessed and compared with that for the thromboxane A2-mimetic U46619 and prostaglandin F2 alpha (PGF2 alpha). All substances caused significant increases in pressure, ET-1 being the most potent, followed in order by U46619, ET-3 and PGF2 alpha. In addition, ET-like immunoreactivity was identified in the fetal effluent of placental lobules during 4 h of basal perfusion. The mean ET-1 equivalent immunoreactivity at 1 h of perfusion was 0.6 +/- 0.2 fmol min-1 g-1 of wet lobule weight for 10 placentae. These data suggest that human fetal placental endothelial cells are capable of synthesizing ETs and that ETs are potent constrictors of the fetal placental vessels. Thus, endothelins may play a role in the control of fetal vascular tone in the human placenta in normal and/or pathological conditions.