EFFECT OF ENDOTHELIUM REMOVAL ON PROSTAGLANDIN AND NITRIC-OXIDE FUNCTION IN PULMONARY RESISTANCE ARTERIES IN THE LAMB

We have recently shown that isolated pulmonary resistance arteries of the fetal lamb have prostaglandin (PG) I-2 based and nitric oxide (NO) based relaxing mechanisms, which are activated by oxygen (al neonatal levels) and bradykinin. The present study was carried out to ascertai n whether these mechanisms remain operational after removal of the end othelium. Endothelium-denuded Vessels pre-equilibrated at a neonatal P O2 were not affected by indomethacin (2.8 mu M), while they contracted weakly to N-G-nitro-L-arginine methyl eater (L-NAME, 100 mu M) Howeve r, the latter response did not reach significance and resembled that o f intact vessels at fetal PO2. Bradykinin (0.1-100 nM) dose dependentl y (from 1-3 nM upwards) relaxed endothelium-denuded arteries that had been precontracted with a thromboxane (TX) A(2) analog (ONO-11113, 0.1 mu M) or excess potassium (5 mM Ca2+ in K+-Krebs) at a neonatal PO2. The response was the same under the two conditions, but it was smaller than that of intact arteries. Bradykinin relaxation of ONO-11113-cont racted arteries was completely or nearly completely inhibited by indom ethacin and L-NAME. We conclude that endothelium-denuded, pulmonary re sistance arteries maintain PG (conceivably PGI(2)) mediated and NO-med iated relaxing mechanisms. These extra-endothelial mechanisms are acti vated by bradykinin but not by oxygen.