Background:Cardiovascular dysfunction at birth may underlie poor outcomes after fetal growth restriction (FGR) in neonates. We compared the cardiovascular transition between FGR and appropriately grown (AG) preterm lambs and examined possible mechanisms underlying any cardiovascular dysfunction in FGR lambs.Methods:FGR was induced in ewes bearing twins at 0.7 gestation; the twin was used as an internal control (AG). At 0.8 gestation, lambs were delivered and either euthanized with their arteries isolated for in vitro wire myography, or ventilated for 2 h. At 60 min, inhaled nitric oxide (iNO) was administered in a subgroup for 30 min. Molecular assessment of the nitric oxide (NO) pathway within lung tissue was conducted.Results:FGR lambs had lower left ventricular output and cerebral blood flow (CBF) and higher systemic vascular resistance compared with AG lambs. INO administration to FGR lambs rapidly improved cardiovascular and systemic hemodynamics but resulted in decreased CBF in AG lambs. Isolated arteries from FGR lambs showed impaired sensitivity to NO donors, but enhanced vasodilation to Sildenafil and Sodium nitroprusside, and altered expression of components of the NO pathway.Conclusion:Cardiovascular dysfunction at birth may underlie the increased morbidity and mortality observed in preterm FGR newborns. Impaired NO signaling likely underlies the abnormal vascular reactivity.