The soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) inhibits relaxation of rabbit aortic rings induced by carbon monoxide, nitric oxide, and glyceryl trinitrate

Carbon monoxide (CO), a vasodilator, has been implicated as an activator of soluble guanylyl cyclase (sGC) to effect smooth muscle relaxation; however, this idea has not received universal support. The purpose of this study was to examine the effects of the sGC inhibitor 1H-[1,2,4]oxadiazolo [4,3-a] quinoxalin-1-one (ODQ) on relaxation of rabbit aortic rings (RARs) induced by CO. Administration of 10 mu M ODQ completely abolished relaxation of RARs by CO (30 mu M), whereas only a partial attenuation of NO-induced relaxation was achieved by the same concentration of ODQ. The results of this study suggest that CO-mediated relaxation of RARs is mediated by sGC and indicate that ODQ may serve as a useful tool in the investigation of the actions of CO. Furthermore, these observations support the idea that ODQ is less potent in inhibiting relaxations by NO, thereby implicating a component of NO-induced relaxation that is independent of sGC/cGMP.