Effect of endothelium removal on prostaglandin and nitric oxide function in pulmonary resistance arteries in the lamb

Abstract

We have recently shown that isolated pulmonary resistance arteries of the fetal lamb have prostaglandin (PG) I2 based and nitric oxide (NO) based relaxing mechanisms, which are activated by oxygen (at neonatal levels) and bradykinin. The present study was carried out to ascertain whether these mechanisms remain operational after removal of the endothelium. Endothelium-denuded vessels pre-equilibrated at a neonatal PO2 were not affected by indomethacin (2.8 µM), while they contracted weakly to NG-nitro-L-arginine methyl ester (L-NAME, 100 µM). However, the latter response did not reach significance and resembled that of intact vessels at fetal PO2. Bradykinin (0.1-100 nM) dose dependently (from 1-3 nM upwards) relaxed endothelium-denuded arteries that had been precontracted with a thromboxane (TX) A2 analog (ONO-11113, 0.1 µM) 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-contracted arteries was completely or nearly completely inhibited by indomethacin and L-NAME. We conclude that endothelium-denuded, pulmonary resistance arteries maintain PG (conceivably PGI2) mediated and NO-mediated relaxing mechanisms. These extra-endothelial mechanisms are activated by bradykinin but not by oxygen.Key words: perinatal pulmonary circulation, endothelium, nitric oxide, prostaglandin, oxygen.