An increase in fetoplacental vascular resistance caused by hypoxia is considered one of the key factors of placental hypoperfusion and fetal undernutrition leading to intrauterine growth restriction (IUGR), one of the serious problems in current neonatology. However, although acute hypoxia has been shown to cause fetoplacental vasoconstriction, the effects of more sustained hypoxic exposure are unknown. This study was designed to test the hypothesis that chronic hypoxia elicits elevations in fetoplacental resistance, that this effect is not completely reversible by acute reoxygenation, and that it is accompanied by increased acute vasoconstrictor reactivity of the fetoplacental vasculature. We measured fetoplacental vascular resistance as well as acute vasoconstrictor reactivity in isolated perfused placentae from rats exposed to hypoxia (10% O(2)) during the last week of a 3-wk pregnancy. We found that chronic hypoxia shifted the relationship between perfusion pressure and flow rate toward higher pressure values (by approximately 20%). This increased vascular resistance was refractory to a high dose of sodium nitroprusside, implying the involvement of other factors than increased vascular tone. Chronic hypoxia also increased vasoconstrictor responses to angiotensin II (by approximately 75%) and to acute hypoxic challenges (by >150%). We conclude that chronic prenatal hypoxia causes a sustained elevation of fetoplacental vascular resistance and vasoconstrictor reactivity that are likely to produce placental hypoperfusion and fetal undernutrition in vivo.

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Important fetal and perinatal pathologies, especially intrauterine growth restriction (IUGR), are thought to stem from placental hypoxia-induced vasoconstriction of the fetoplacental vessels, leading to placental hypoperfusion and thus fetal undernutrition. However, the effects of hypoxia on the fetoplacental vessels have been surprisingly little studied. We review here available experimental data on acute hypoxic fetoplacental vasoconstriction (HFPV) and on chronic hypoxic elevation of fetoplacental vascular resistance. The mechanism of HFPV includes hypoxic inhibition of potassium channels in the plasma membrane of fetoplacental vascular smooth muscle and consequent membrane depolarization that activates voltage gated calcium channels. This in turn causes calcium influx and contractile apparatus activation. The mechanism of chronic hypoxic elevation of fetoplacental vascular resistance is virtually unknown except of signs of the involvement of morphological remodeling.