Fetal ACTH and blood pressure responses to thromboxane mimetic U-46619

This study was performed to test the hypothesis that thromboxane A2 stimulates increases in fetal adrenocorticotropic hormone (ACTH), vasopressin, or renin secretion and affects fetal cardiovascular function by an action on the fetal central nervous system. We infused a stable synthetic analogue of thromboxane A2, U-46619, into one common carotid artery or inferior vena cava or infused saline into one common carotid artery in chronically catheterized fetal sheep between 127 and 140 days gestation. We found that intracarotid but not intravenous infusions of U-46619 at a rate of 750 ng/min stimulated increases in fetal plasma ACTH concentration. Infusions of U-46619 at both sites increased fetal blood pressure; the infusion into the carotid arterial blood produced a more rapid increase in blood pressure and a significant decrease in central venous pressure. None of the infusions altered plasma vasopressin concentration or plasma renin activity, blood gases, hematocrit, or plasma cortisol concentration. We conclude that thromboxane A2 stimulates fetal ACTH, but not vasopressin or renin, secretion via an action within the area perfused by carotid arterial blood. Thromboxane A2 increases blood pressure via an action at the fetal central nervous system, as well as via a direct vasoconstrictor action in the systemic circulation.