Effect of in vivo fetal infusion of dexamethasone at 0.75 GA on fetal ovine resistance artery responses to ET-1

At 110-111 days gestation, instrumented fetal sheep were administered saline or dexamethasone (2.2 mug.kg(-1).h(-1) iv) for 48 h. Measurement of fetal blood pressure showed a greater increase in dexamethasone-treated (n = 6) compared with control (n = 5) fetuses (7.3 +/- 2.3 vs. 0.6 +/- 2.3 mmHg, P< 0.05). Fetuses were delivered by cesarean section, and the femoral muscle and brain were obtained under halothane anesthesia. Femoral and middle cerebral arteries (<similar to>320-mum internal diameter) were evaluated using wire myography. Sensitivity to KCl (2.5-125 mM) and the magnitude of the maximal vasoconstriction to 125 mM K+ were similar in femoral and middle cerebral arteries from dexamethasone-treated vs. control fetuses. Acetylcholine-induced vasorelaxation was similar in femoral arteries from control and dexamethasone-treated fetuses. Middle cerebral arteries did not relax to acetylcholine. Sensitivity to endothelin-1 (ET-1; 0.1 pM-0.1 muM) and magnitude of the ET-1-induced vasoconstriction were greater in femoral arteries from dexamethasone-treated vs. control fetuses (P< 0.05). Autoradiographical studies with receptor-specific ligands demonstrated increased ETA-receptor binding, the principal receptor subtype, in femoral muscle vessels (P< 0.001) but decreased ETA-receptor binding in middle cerebral arteries (P< 0.01) from dexamethasone-treated compared with control fetuses. Relatively little ETB-receptor binding was evident in all tissues examined. We conclude that hyperreactivity to ET-1, due to increased ETA-receptor binding, may be involved in the dexamethasone-induced increase in peripheral vascular resistance in fetal sheep in vivo.