Hypoxia augments conversion of big-endothelin-1 and endothelin ET(B) receptor-mediated actions in rat lungs.
We have examined the effect of endothelin-1, sarafotoxin-6C, big-endothelin-1 and other agents on perfused lungs from chronically hypoxic rats. Increases in pulmonary perfusion pressure induced by big-endothelin-1, endothelin-1, phenylephrine and potassium chloride were enhanced in hypoxic lungs, while the constrictor action of sarafotoxin-6C was not increased. When basal pulmonary perfusion pressure was raised, low doses of endothelin-1 and sarafotoxin-6C produced decreases in pulmonary perfusion pressure which were significantly greater in chronically hypoxic lungs, whereas responses to sodium nitroprusside were unchanged. Endothelin ET(B) receptor-mediated bronchoconstrictor responses were also potentiated in hypoxic lungs, whereas responses to carbachol were not. In hypoxic lungs, conversion of big-endothelin-1 to endothelin-1 was significantly increased. These data provide evidence for a generalised increase in vasomotor activity in chronically hypoxic lungs, and a more selective increase in endothelin ET(B) receptor-mediated vasodilator and bronchoconstrictor responses. Hypoxia also augments the conversion of big-endothelin-1 to endothelin-1.
Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath BA2 7AY, UK
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Lal
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Yu
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Ivor Williams
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Woodward
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D019332:Endothelin-1 / Q000494:pharmacology; D016232:Endothelins / Q000378:metabolism* / Q000494:pharmacology; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism*; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011498:Protein Precursors / Q000378:metabolism* / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000187:drug effects / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology
D019332:Endothelin-1; D016232:Endothelins; D018721:Muscarinic Agonists; D011498:Protein Precursors; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; D009599:Nitroprusside; D010656:Phenylephrine; D011189:Potassium Chloride; D002217:Carbachol