Document Detail

Hypoxia induces the release of a pulmonary-selective, Ca(2+)-sensitising, vasoconstrictor from the perfused rat lung.
MedLine Citation:
PMID:  11282087     Owner:  NLM     Status:  MEDLINE    
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.
T P Robertson; J P Ward; P I Aaronson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cardiovascular research     Volume:  50     ISSN:  0008-6363     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2001 Apr 
Date Detail:
Created Date:  2001-04-03     Completed Date:  2001-06-07     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  145-50     Citation Subset:  IM    
Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, 30602, USA.
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MeSH Terms
Acetonitriles / pharmacology
Anoxia / metabolism*
Calcium / metabolism*
Dinoprost / pharmacology
Endothelin-1 / physiology
Enzyme Inhibitors / pharmacology
Indoles / pharmacology
Ion Channel Gating / physiology
Lung / blood supply,  metabolism*
Organ Culture Techniques
Protein Kinase C / antagonists & inhibitors,  physiology
Pulmonary Artery / drug effects,  physiology
Vasoconstriction / drug effects,  physiology
Vasoconstrictor Agents / metabolism*
Reg. No./Substance:
0/Acetonitriles; 0/Endothelin-1; 0/Enzyme Inhibitors; 0/Indoles; 0/Vasoconstrictor Agents; 125314-64-9/Ro 31-8220; 551-11-1/Dinoprost; 7440-70-2/Calcium; 75-05-8/acetonitrile; EC Kinase C

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