Fetal cerebral oxygenation: the homeostatic role of vascular adaptations to hypoxic stress.

The mammalian fetus is highly adapted for growth in a low-O(2) environment in which arterial O(2) tensions average near 30 mm Hg. Acute decreases in O(2) tension below this value elicit vasodilatation, but the responses are blunted compared to those observed in adults. Chronic hypoxia in the fetus stimulates a pattern of cerebrovascular remodeling that results in an increased wall thickness and decreased overall contractility and also depresses the capacity for cerebral vasodilatation through decreases in NO release, soluble guanylate cyclase activity, and expression of PKG substrates. Many of these hypoxic effects appear to be homeostatic and may be mediated by VEGFs, which increase in direct response to hypoxia and, in turn, can dramatically alter the expression and function of multiple contractile proteins in cerebrovascular smooth muscle through both endothelium-dependent and endothelium-independent effects on large artery smooth muscle.