Endothelin-1 does not mediate acute hypoxic pulmonary vasoconstriction in the intact newborn lamb

J. Wong, P. A. Vanderford, J. W. Winters, R. Chang, S. J. Soifer, J. R. Fineman

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

The mechanisms by which acute alveolar hypoxia induces pulmonary vasoconstriction remain unclear. Previous studies suggest that hypoxia- induced vasoconstriction is endothelium-dependent and is associated with the release of endothelin-1 (ET-1), a potent vasoactive paracrine hormone produced by vascular endothelial cells. The vasoconstrictive effects of ET-1 are likely to be mediated by ET(A) receptors located on vascular smooth- muscle cells. BQ-123 is a selective ET(A) receptor antagonist. To determine the role of ET-1 and ET(A) receptors on resting tone and hypoxic pulmonary vasoconstriction, we studied the effects of ET-1 and BQ-123 at rest and during hypoxia-induced pulmonary vasoconstriction in 12 intact newborn lambs (<1 week old). At rest, the intrapulmonary infusion of BQ-123 did not change resting pulmonary arterial pressure but completely blocked the rapid increase in pulmonary artery pressure produced by high doses of ET-1 (2,000 ng/kg) (23.0 ± 10.8% versus -12.6 ± 27.5%; p<0.05). During mechanical ventilation there was no difference in the increase in mean pulmonary arterial pressure and pulmonary vascular resistance induced by alveolar hypoxia before and after BQ-123 (34.0 ± 8.9% versus 30.5 ± 10.9% and 25.3 ± 11.6% versus 35.2 ± 22.4%). This study suggests that the pulmonary vasoconstrictive effects of ET-1 are mediated by ET(A) receptors and that ET-1 does not mediate acute hypoxic pulmonary vasoconstriction in intact newborn lambs.

Original languageEnglish (US)
Pages (from-to)S262-S266
JournalJournal of Cardiovascular Pharmacology
Volume22
Issue numberSUPPL. 8
DOIs
StatePublished - 1993

Keywords

  • Endothelin receptors
  • Endothelin-1
  • Pulmonary vasoconstriction

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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