Effect of chronic hypoxia on endothelium-dependent relaxation and cGMP content in rat pulmonary artery

This experiment was designed to determine whether chronic hypoxia affects endothelium-dependent relaxation and cGMP content of rat pulmonary artery (PA). Both Ach and ATP were found to induce endothelium-dependent relaxation of PA; and this relaxation was not prevented by indomethacin, but was completely abolished by methylene blue. Chronic hypoxia significantly depressed the endothelium-dependent relaxation: the relaxation responses of intra-PA (IPA) and extra-PA (EPA) to 10(-6) mol/L Ach in the hypoxic group were 61.3% and 59.2% of those in control, and the relaxation responses of IPA and EPA to 1.8 x 10(-5) mol/L ATP in the hypoxic group were 64.9% and 55.2% of those in the control, respectively. Chronic hypoxia significantly decreased the basic level and Ach-induced accumulation of cGMP in the PA. Our data suggest that chronic hypoxia might depress rat pulmonary artery endothelium-dependent relaxation through the inhibition of cytosolic soluble guanylate cyclase in vascular smooth muscle cells.