REGULATION OF PLACENTAL VASCULAR REACTIVITY IN PIH

Project: Research project

Project Details

Description

Pregnancy-induced hypertension (PIH) is associated with increased
fetal and neonatal morbidity and mortality possibly resulting from
hypoxia in utero. The primary pathology of PIH involves a
reduction in uteroplacental blood flow but modern imaging
techiques have now shown that increased impedance of the fetal-
placental circulation and hence reduced blood flow can also be
found in PIH. This may represent a direct effect of hypoxia or be
a fetal adaptation to increase placental oxygen extraction to
relieve hypoxia. The fetal-placental circulation is regulated by
humoral agents and vascular pressure. An imbalance of
vasodilator prostacyclin (PGI2) and vasoconstrictor thromboxane
(TxA2) production is reported to underlie the vasoconstriction
seen in PIH. We will commence with the premise that there is an imbalance of
PGI2 and TxA2 in PIH. We will establish in the fetal-placental
circulation of the perfused human placental cotyledon from both
normotensive and PIH pregnancies:
1. If such an imbalance in PGI2/TxA2 production exists
2. Its relationship to the responses of the fetal-placental
circulation to vasoconstrictors
3. The effect of increasing fetal-placental flow on PGI2
production and responses to vasoconstrictors.
4. The effects of hypocalcemia and hypomagnesemia on PGI2
synthesis and if supplementation with these cations alters
responses to vasoconstrictors
5. If hypoxia reduces PGI2 synthesis or angiotensin converting
enzyme activity and so alters vascular reactivity
6. Whether there is an increase in lipoxygenase product
(leukotriene) formation linked to the deficiency in PGI2 synthesis
7. If drugs now used to restore the PGI2/TxA2 balance in PIH
may cross the placenta and alter umbilical vascular reactivity. Our primary objective is to elucidate the potential role an
imbalance in PGI2/TxA2 may have in controlling the vascular
reactivity of the fetal/placental circulation, what the underlying
mechanisms are behind the PGI2/TxA2 imbalance and how
therapeutic agents may affect this to improve blood flow and
reduce fetal morbidity and mortality.
StatusFinished
Effective start/end date9/30/877/31/92

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $117,849.00
  • National Institutes of Health

ASJC

  • Medicine(all)

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