INTERACTION AMONG ET-1, ENDOTHELIUM-DERIVED NITRIC-OXIDE, AND PROSTACYCLIN IN PULMONARY-ARTERIES AND VEINS

Endothelin-1 causes vasodilation of the intact porcine pulmonary vascu lar bed. To determine the cause of this vasodilation, we investigated the interactions of endothelin-1 (ET-1), endothelium-derived nitric ox ide (EDNO), and prostacyclin in isolated small porcine pulmonary arter ies and veins under in vitro conditions. ET-1 caused concentration-dep endent contractions in arteries and veins, augmented by the nitric oxi de synthase (NOS) inhibitor, N-omega-nitro-L-arginine, in pulmonary ve ins. BQ-123 (ET(A)-receptor antagonist) depressed the ET-1-induced con tractions. Sarafotoxin S6C, an ET(B)-receptor agonist, caused contract ions of pulmonary veins only. Endothelium-dependent relaxations to bra dykinin and ET-1 were greater in pulmonary veins compared with arterie s, inhibited by N-omega-nitro-L-arginine, and reversed by L-arginine. BQ-123 augmented ET-1-induced arterial relaxation. ET-3 and sarafotoxi n S6C, ET(B)-receptor agonists, caused comparable endothelium-dependen t relaxations in arteries and veins. ET-1 caused a fourfold greater in crease in prostacyclin release in pulmonary veins compared with arteri es. We conclude that ET-1 is a potent vasoconstrictor of porcine pulmo nary vessels and stimulates the release of EDNO and prostacyclin, whic h oppose the contractions to the peptide. The release of these endothe lium-derived vasodilators appears greater in pulmonary veins.