Aims: 

Despite its crucial importance in fetal physiology and pathology, the regulation of fetoplacental vasculature is poorly understood. Based on similarity in function with the adult pulmonary circulation we hypothesized that acute hypoxia elicits fetoplacental vasoconstriction by mechanisms similar to those known in the pulmonary vessels. We also proposed that chronic hypoxia produces morphological and functional changes in the fetoplacental vasculature analogous to chronic hypoxic pulmonary hypertension.

Methods: 

We used isolated perfused cotyledon of human placenta, isolated perfused rat placenta, isolated fetoplacental vessels and their smooth muscle cells, and morphological methods.

Results: 

Acute hypoxia causes marked fetoplacental vasoconstriction by inhibiting voltage-gated K⁺ channels and subsequent Ca²⁺ influx completely carried by L-type Ca²⁺ channels. Chronic hypoxia in the rat (10% O₂ during the last week of the 3-week pregnancy) elevated fetoplacental vascular resistance and increased reactivity to vasoconstrictor stimuli (acute hypoxic challenge and angiotensin II). Morphologically, we found a random mixture of increased and reduced wall thickness of peripheral fetoplacental vessels in chronic hypoxia. The average lumen diameter, however, was consistently reduced.

Conclusions: 

We conclude that fetoplacental vessels, particularly their smooth muscle cells, are exquisitely responsive to hypoxia. Their response to acute hypoxia is rather similar to that in the pulmonary circulation. The response to chronic hypoxia does not include the marked thickening of the vascular wall typical for hypoxic pulmonary hypertension; nevertheless, it does result in reduced lumen area and increased vascular resistance. It is likely that this mechanism significantly contributes to serious neonatal disorders such as intrauterine growth restriction.