Oral Presentation 46th Annual Meeting of the Fetal and Neonatal Physiological Society 2019
Antenatal glucocorticoid therapy (AGT) protects the chronically hypoxic fetus from programmed endothelial dysfunction and hypertension in adulthood (#7)
Background: AGT reduces respiratory distress and death in preterm infants. Despite benefits, AGT may programme adverse cardiovascular function in the offspring. This knowledge is mostly derived from studies in healthy animals, with comparatively little known in those from complicated pregnancy. We isolated the long-term effects of AGT on cardiovascular function at adulthood in sheep, which were born at term and were either normally grown or IUGR due to chronic hypoxia.
Method: From 0.7 of gestation, pregnant ewes were exposed to normoxia (N) or chronic hypoxia (H, 10% O2 maternal inspired air) followed by AGT (0.8 gestation; 2x12mg dexamethasone (D) maternal i.m. 24h apart) or saline vehicle. A week before natural delivery, all hypoxic pregnancies returned to normoxia. Offspring were maintained under normoxia until 9 months, then chronically instrumented under anaesthesia to determine in vivo cardiovascular physiology and ex vivo femoral endothelial function with wire myography. Data were analysed by 2-way ANOVA, P<0.05.
Results: Offspring of hypoxic pregnancy were smaller at birth (A) and hypertensive (B) with peripheral endothelial dysfunction (C) at adulthood. AGT in hypoxic pregnancy restored the programmed hypertension via mechanisms including enhanced NO biology. Offspring of AGT hypoxic pregnancy had a greater fall in femoral vascular conductance (FVC) during in vivo NO blockade (D) and protection against endothelial dysfunction (C) at adulthood.
Conclusions: AGT in clinically relevant doses protects the chronically hypoxic IUGR fetus from programmed hypertension by increasing NO bioavailability and improving peripheral endothelial function.
Support: BHF
