Role of endothelium in biphasic hypoxic response of the isolated pulmonary artery in the rat

We investigated the roles of the endothelium in the hypoxic responses of the isolated main pulmonary artery (PA) in the rat. Hypoxia was induced by gas-sing an organ chamber with 95% N2+5% CO2 (P02=34.6±3.1 Torr) instead of 16% O2+5% CO2+balance N2 (PO2=92.8±3.0 Torr). Vascular rings were precontracted with 2×10-8 M phenylephrine. A transient hypoxic contraction and a subsequent relaxation were observed in the endothelium-intact rings. The hypoxic contraction was reduced in the endothelium-denuded rings. In contrast, there were no significant differences between the hypoxic relaxation in the endothelium-intact and endothelium-denuded rings. Inhibitors of endothelium-derived relaxing factor (EDRF) activity, 2×10-6 M NG-monomethyl-L-arginine (L-NMMA) and 10-6 M methylene blue, produced 53% and 66% reductions in hypoxic contraction, respectively, Furthermore, the amount of cyclic GMP in the endothelium-intact PA rings which had been precontracted with phenylephrine decreased from 2. 10±0.45 pmol/mg protein during normoxia to 0.90±0.18 pmol/mg protein during hypoxia. Indomethacin and OKY-046 did not influence hypoxic contraction or relaxation. These results suggest that hypoxic contraction of the isolated pulmonary artery in the rat is partially induced by inhibition of the release of EDRF.