ENDOTHELIN ET(A)-RECEPTOR-MEDIATED AND ET(B)-RECEPTOR-MEDIATED VASOCONSTRICTION IN RAT PULMONARY-ARTERIES AND ARTERIOLES

We investigated the endothelin (ET) receptors involved in the vasocons trictor responses to ET-1 in rat pulmonary arteries and arterioles and the effect of endothelium removal, nitric oxide (NO) synthase inhibit ion, and hypoxia on ET-1-induced responses in the arteries. In isolate d rat pulmonary artery rings (2-3 mm ID) prepared from the pulmonary a rtery branch before its entry into the lung, ET-1-induced vasoconstric tor responses. These responses were mediated by the ET(A) receptor as they were competitively antagonized by the ET(A) receptor antagonist F R 139317, and the ET(B)-receptor agonist sarafotoxin S6c (SXS6c) was a very weak vasoconstrictor in these vessels, inducing maximum contract ions only 9% of those of ET-1. In contrast, in rat intrapulmonary resi stance arteries (100-150 mu m ID), SXS6c induced FR 139317-resistant c ontractions, and these vessels were more sensitive to SXS6c than to ET -1. SXS6c produced maximum contractions 92% those of ET-1, suggesting that ET-1-induced contractions were mediated by the ET(A) receptor in these resistance vessels. In the larger pulmonary arteries, the NO syn thase inhibitor L-N-omega nitroarginine methyl ester (L-NAME) (100 mu M) potentiated responses to ET-1, an effect that was reversed by FR 13 9317. Endothelium removal also potentiated response to ET-1, and L-NAM E had no effect on ET-1 responses in endothelium-denuded vessels, sugg esting that in these vessels the ET(A) receptor-mediated responses to ET-1 are normally suppressed by endothelium-derived NO. Hypoxia did no t affect the sensitivity of the vessels to ET-1, but did increase the ability of FR 139317 to antagonise these responses. L-NAME did not aff ect responses to SXS6c in pulmonary resistance vessels.