Novel endothelial-derived vasoactive factors in the human fetal-placental circulation

Leslie Myatt, Anthony S. Brewer, Gretchen Langdon, Diane E. Brockman

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

The role of novel endothelial-cell derived relaxing and contracting factorshave been investigated in the perfused human placental cotyledon. By using specific inhibitors of synthesis of the relaxing factor, nitric oxide, we have found that nitric oxide synthesis and action appears to contribute to maintenance of basal tone in the human fetal-placental circulation and attenuates the vasoconstrictor actions of thromboxane A2 and the peptide endothelin-1. Endothelin-1 is a potent long acting vasoconstrictor (8×10−10–1×10−8M) in the human fetal-placental circulation. The duration of action and potency make it unlikely to have an acute vasoconstrictor role, but rather it may act to contribute towards basal tone or to potentiate the action of other vasoconstrictors. Although it has been suggested that Et-1 releases thromboxane A2 in the fetal-placental circulation and this mediates the Et-1-induced vasoconstriction, we have shown that Et-1-induced vasoconstriction results in a significant reduction in thromboxane release, probably due to the reduction in flow rate. Further, by using a thromboxane synthase inhibitor, dazoxiben, or a thromboxane receptor antagonist, SQ29548, we have conclusively shown that Et-1 vasoconstriction is not mediated via thromboxane synthesis and action. NO does not appear to be released by the classic EDRF agonists such as acetylcholine, bradykinin, histamine, or calcium ionophores in the fetal-placental circulation. Indeed, bradykinin is a vasoconstrictor in this circulation and the concentrations of histamine necessary to cause vasodilation are in excess of those shown to release EDRF in other systems. Rather the stimulus to NO release in the placenta may be transmural pressure and/or flow/shear stress across endothelium.

Original languageEnglish (US)
Pages (from-to)117-131
Number of pages15
JournalPlacenta
Volume14
DOIs
StatePublished - 1993
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology
  • Developmental Biology

Cite this