Evidence for oxygenation-induced endothelin release from isolated lungs ofchronically hypoxic rats

In lungs from chronically hypoxic (CH, 3 weeks at 10% inspired O-2) rats, o xygenation (20% O-2, 5% CO2, 75% N-2; P-o2 121 mmHg) of the perfusate incre ases pulmonary perfusion pressure (PPP) and lung weight (LW). Hypoxic perfu sate (95% N-2, 5% CO2; P-o2 5.5 mmHg) had no effect on PPP in lungs from CH rats. Indomethacin and nitro-L-arginine (L-NOARG) augmented the oxygen-ind uced increase in PPP. In contrast, the free radical scavengers superoxide d ismutase (SOD) plus catalase delayed the onset of oxygen-induced vasoconstr iction, while the endothelin (ET)(B) receptor antagonist BQ788 inhibited it . The ETA receptor antagonist BQ123 did not affect the PPP changes. This su ggests a role for endogenous endothelins and ETB receptors in mediating the oxygenation-induced pulmonary vasoconstriction. Indomethacin had no effect on oxygen-induced lung weighs (LW) changes while BQ788 and L-NOARG reduced the LW increase. This evidence shows that ETB receptor activation and NO g eneration are involved in the LW changes. In conclusion, oxygenation of the perfusate in isolated lungs from CH rats leads to pulmonary vasoconstricti on which involves endothelins and activation of ETB receptors. In addition, increased NO production associated with ETB receptor. activation is the pr ime stimulus for observed LW increase. (C) 1999 Elsevier Science B.V. All r ights reserved.