Soluble guanylate cyclase redox state under hypoxia or hypoxia/ reoxygenation in isolated monkey coronary arteries

Hypoxia or hypoxia/reoxygenation impairs nitric oxide (no)-mediated relaxation through the increase in superoxide generation in monkey coronary arteries. soluble guanylate cyclase (sgc),the target enzyme of no,has been shown to change from the no-sensitive reduced form to the no-insensitive oxidized/heme-free form under substantial oxidative stress,so the present study investigated whether hypoxia or hypoxia/reoxygenation influences sgc redox equilibrium. in isolated monkey coronary arteries without endothelium,the relaxation caused by the sgc stimulator bay 41-2272 (emax: 93.3% ± 2.2%) was somewhat impaired under hypoxia (emax: 86.3% ± 2.6%) or hypoxia/reoxygenation (emax: 86.1% ± 3.2%),whereas that by the sgc activator bay 60-2770 (emax: 86.0% ± 3.2%) was significantly augmented under hypoxia (emax: 94.4% ± 1.3%) or hypoxia/reoxygenation (emax: 95.5% ± 1.1%). in addition,cgmp formation in response to bay 41-2272 and bay 60-2770 was inhibited and stimulated,respectively,under hypoxia or hypoxia/reoxygenation. the effects of hypoxia or hypoxia/reoxygenation on bay 41-2272- and bay 60-2770-induced vasorelaxation were completely canceled by the treatment with the superoxide dismutase mimetic tempol. these findings suggest that sgc redox equilibrium in the coronary artery is shifted towards the no-insensitive form under hypoxia or hypoxia/reoxygenation and that superoxide seems to play an important role in this shift. © the japanese pharmacological society.