REGULATION OF ATRIAL-NATRIURETIC-FACTOR RELEASE BY ENDOTHELIN IN OVINE FETUSES

Endothelin is a potent vasoconstrictor synthesized by vascular endothelial cells. In the adult, endothelin has been shown to stimulate the release of atrial natriuretic factor (ANF) through a direct action on atrial cardiocytes. The present study was designed to investigate, in the fetus, whether endothelin would similarly release ANF into the circulation. In addition, the effects of endothelin on fetal cardiovascular and urinary functions were explored. Chronically catheterized ovine fetuses between 126 and 139 days gestation (term 147 days) were used for the study. After a 30-min control period, the fetuses were infused intravenously with vehicle (n = 6) or endothelin-1 (n. = 9) at 25 ng.min(-1) kg(-1) for 30 min, and this was followed by a 60-min recovery period. In response to endothelin infusion, plasma ANF levels were significantly elevated. Endothelin infusion acutely increased fetal arterial pressure without affecting venous pressure. Fetal heart rate decreased, and blood volume was reduced. Fetal urine flow rate and urinary excretion of electrolytes did not change during the endothelin infusion but were elevated during the recovery period. The fetus developed hypoxia and acidemia. Thus our study demonstrates that endothelin is effective in stimulating ANF release in the fetus, and this effect appears to be unrelated to the venous pressure changes. In addition, the results suggest that endothelin is a potent vasoconstrictor of the fetal systemic and umbilical vascular beds. The decrease in blood volume and increase in urinary excretion of fluid and electrolytes in response to endothelin are consistent with the known actions of ANF, which is elevated during endothelin infusion.