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


CONCLUSIONS
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.
Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, 30602, USA. troberts@vet.uga.edu
T P
TP
Robertson
J P
JP
Ward
P I
PI
Aaronson
D000097:Acetonitriles / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015237:Dinoprost / Q000494:pharmacology; D019332:Endothelin-1 / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000860:Hypoxia / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D015640:Ion Channel Gating / Q000502:physiology; D008168:Lung / Q000098:blood supply / Q000378:metabolism*; D008297:Male; D009924:Organ Culture Techniques; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology; D051381:Rats; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000378:metabolism*
D000097:Acetonitriles; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D007211:Indoles; D014662:Vasoconstrictor Agents; D015237:Dinoprost; D011493:Protein Kinase C; D002118:Calcium; C064758:Ro 31-8220; C032159:acetonitrile