Hypoxia augments conversion of big-endothelin-1 and endothelin ETB 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. Increa ses in pulmonary perfusion pressure induced by big-endothelin-1, endothelin -1, phenylephrine and potassium chloride were enhanced in hypoxic lungs, wh ile the constrictor action of sarafotoxin-6C was not increased. When basal pulmonary perfusion pressure was raised, low doses of endothelin-1 and sara fotoxin-6C produced decreases in pulmonary perfusion pressure which were si gnificantly greater in chronically hypoxic lungs, whereas responses to sodi um nitroprusside were unchanged. Endothelin ETB receptor-mediated bronchoco nstrictor responses were also potentiated in hypoxic lungs, whereas respons es to carbachol were not. In hypoxic lungs, conversion of big-endothelin-1 to endothelin-1 was significantly increased. These data provide evidence fo r a generalised increase in vasomotor activity in chronically hypoxic lungs , and a more selective increase in endothelin ETB receptor-mediated vasodil ator and bronchoconstrictor responses. Hypoxia also augments the conversion of big-endothelin-1 to endothelin-1. (C) 2000 Elsevier Science B.V. All ri ghts reserved.