Modulatory role of EDRF in hypoxic contraction of isolated porcine pulmonary arteries.

To examine the hypothesis that suppression of basal release of endothelium-derived relaxing factor (EDRF) by hypoxia might be related to the mechanism of hypoxic pulmonary vasoconstriction, rings of porcine pulmonary artery (PA, 2 mm OD) were suspended in organ chambers and changes in isometric force were measured. Hypoxia significantly reduced endothelium-dependent relaxation induced by acetylcholine and augmented contractile response to phenylephrine. This augmentation by hypoxia was not seen in rings without endothelium. Contractile response to phenylephrine was also enhanced by removal of endothelium. With 15 min of hypoxia, PA contracted and guanosine 3',5'-cyclic monophosphate content decreased. Pretreatment with 10(-6) M methylene blue, 3 x 10(-7) M oxyhemoglobin, and 9.6 x 10(-5) M NG-monomethyl-L-arginine significantly enhanced hypoxic contraction. Furthermore, removal of endothelium also enhanced hypoxic contraction. These results suggest that suppression of basally released EDRF by hypoxia was not the cause of the contractile response to hypoxia and that EDRF modulates the hypoxic contraction of porcine PA in basal conditions at this diameter.