Hypoxic pulmonary endothelial cells release a diffusible contractile factor distinct from endothelin

Sean P. Gaine, Mariesa A. Hales, Nicholas A. Flavahan

Research output: Contribution to journalArticle

Abstract

Hypoxia (0% O2) evokes a late-phase, endothelium-dependent contractile response in porcine isolated pulmonary arteries that may be caused by a cyclooxygenase-independent, endothelium-derived contractile factor. The aim of this study was to further analyze the mechanism underlying this hypoxic response. Proximal porcine pulmonary arterial rings were suspended for isometric tension recording in organ chambers. Hypoxia (0% O2) caused a late-phase, endothelium-dependent contractile response that was not inhibited by the endothelin (ET)(A)-receptor antagonist BQ-123 (10-6 M), by the ET(B)-receptor antagonist BQ-788 (10-7 M), or by their combination. In contrast, ET-1 caused a concentration-dependent contraction of arterial rings that was inhibited by BQ-123 (10-6 M) and a relaxation that was abolished by BQ-788 (10-7 M) or by endothelial cell removal. Therefore, the endothelium-dependent contraction to hypoxia is not mediated by ET. Hypoxia caused only relaxation in endothelium-denuded rings. However, when a pulmonary valve leaflet, a rich source of pulmonary endothelial cells, was placed into the lumen of endothelium-denuded rings, hypoxia caused a late- phase contractile response that was similar to that observed in arterial rings with native endothelium. This hypoxic contraction persisted in the presence of indomethacin (10-5 M) and N-nitro-L-arginine methyl ester (3 X 10-5 M) to block cyclooxygenase and nitric oxide synthase, respectively. These results suggest that hypoxic contraction of pulmonary arteries is mediated by a diffusible, contractile factor released from hypoxic endothelial cells. This contractile mediator is distinct from ET.

Original languageEnglish (US)
Pages (from-to)L657-L664
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume274
Issue number4 18-4
DOIs
StatePublished - Apr 1998

Keywords

  • Endothelin(A) receptor
  • Endothelin(B) receptor
  • Endothelium
  • Endothelium-derived contractile factor
  • Hypoxia
  • Pulmonary artery
  • Pulmonary valve leaflet

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Fingerprint Dive into the research topics of 'Hypoxic pulmonary endothelial cells release a diffusible contractile factor distinct from endothelin'. Together they form a unique fingerprint.

Cite this