© 2001 by European Society of Cardiology
Copyright © 2001, European Society of Cardiology
Hypoxia induces the release of a pulmonary-selective, Ca2+-sensitising, vasoconstrictor from the perfused rat lung
aDepartment of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, 30602, USA
bDepartment of Respiratory Medicine and Allergy, GKT School of Medicine, King's College London, Guy's Campus, London SE1 9RT, UK
* Corresponding author. Tel.: +1-706-542-3014; fax: +1-706-542-3015 troberts{at}vet.uga.edu
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 Ca2+ channels, and was not associated with a rise in intracellular [Ca2+], suggesting Ca2+-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 F2
. 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 Ca2+ sensitisation, is independent of voltage-gated Ca2+ entry, and is potentiated by the presence of preconstriction.
KEYWORDS Arteries; Caclium (cellular); Hypoxia/anoxia; Pulmonary circulation; Vasoactive agents
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