DOES THROMBOXANE MEDIATE THE FETAL ACTH RESPONSE TO ACIDEMIA

Intravenous mineral acid infusions into fetal sheep stimulate increase s in plasma adrenocorticotropic hormone (ACTH) and cortisol concentrat ions that correlate to the induced changes in arterial pH (pH(a)). We have recently demonstrated that ACTH and cortisol responses to mineral acid infusion in adult sheep are mediated by thromboxane A(2) (TxA(2) ). We designed the present experiments to test the hypothesis that fet al ACTH and cortisol responses are also mediated by TxA(2). We infused chronically instrumented fetal sheep with 1 N HCl (0.5 ml/min iv) for 60 min, with or without pretreatment with the cyclooxygenase inhibito r flunixin-N-methylglucamine. HCl infusion significantly decreased pH( a) and significantly increased the arterial partial pressure of O-2 (P a-O2) and CO2 (Pa-CO2) Flunixin pretreatment significantly decreased f etal plasma thromboxane B-2 (TXB(2)) concentrations but did not signif icantly alter the blood gas and pH response to HCl. TxB(2) is a stable metabolite of TxA(2) and was measured as an index of TxA(2) generatio n. HCl increased fetal heart rate only in the flunixin group. Plasma A CTH and cortisol concentrations were increased significantly in both g roups; flunixin did not significantly alter the responses. HCl infusio n did not significantly alter plasma TxB(2) concentrations. We conclud e that the fetal ACTH and cortisol responses to HCl infusion are not m ediated by TxA(2) or other prostanoids whose synthesis depends on cycl ooxygenase activity.