Hypoxia induces the release of a pulmonary-selective, Ca(2+)-sensitising, vasoconstrictor from the perfused rat lung

Cardiovasc Res. 2001 Apr;50(1):145-50. doi: 10.1016/s0008-6363(01)00192-4.

Abstract

Objective: Sustained hypoxic pulmonary vasoconstriction is dependent upon the presence of an intact endothelium, strongly suggesting that an endothelium-derived constrictor factor is involved in this response. In the present study we have attempted to determine whether hypoxia induces the release of a vasoconstrictor(s) from the lung, and whether this vasoconstrictor shares mechanistic features with the hypoxic constrictor response.

Methods: The salt-perfused rat lung, coupled with a simple solid-phase extraction process, and a rat intrapulmonary artery functional bioassay were utilised in this study.

Results: Hypoxic, but not normoxic, perfusion of the isolated lung of the rat induced the release of a vasoconstrictor(s) which appeared to be selective for pulmonary over mesenteric arteries of the rat. The vasoconstriction observed was unaffected by inhibition of voltage-gated Ca(2+) channels, and was not associated with a rise in intracellular [Ca(2+)], suggesting Ca(2+)-sensitisation of the contractile apparatus. The vasoconstriction was also unaffected by the protein kinase C (PKC) inhibitor Ro-31-8220, or the endothelin-1 antagonists BQ123/BQ788 but was markedly potentiated in the presence of prostaglandin F(2alpha).

Conclusion: We conclude that hypoxic perfusion of the rat lung results in the release of a vasoconstrictor(s) which shares some of the facets of the sustained hypoxic constriction of isolated intrapulmonary arteries of the rat, since it involves PKC-independent Ca(2+) sensitisation, is independent of voltage-gated Ca(2+) entry, and is potentiated by the presence of preconstriction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetonitriles / pharmacology
  • Animals
  • Calcium / metabolism*
  • Dinoprost / pharmacology
  • Endothelin-1 / physiology
  • Enzyme Inhibitors / pharmacology
  • Hypoxia / metabolism*
  • Indoles / pharmacology
  • Ion Channel Gating / physiology
  • Lung / blood supply
  • Lung / metabolism*
  • Male
  • Organ Culture Techniques
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / physiology
  • Pulmonary Artery / drug effects
  • Pulmonary Artery / physiology
  • Rats
  • Vasoconstriction / drug effects
  • Vasoconstriction / physiology
  • Vasoconstrictor Agents / metabolism*

Substances

  • Acetonitriles
  • Endothelin-1
  • Enzyme Inhibitors
  • Indoles
  • Vasoconstrictor Agents
  • Dinoprost
  • Protein Kinase C
  • Calcium
  • Ro 31-8220
  • acetonitrile