1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) inhibits cyclic GMP-PKG pathway-independent nonadrenergic, noncholinergic relaxation in longitudinal muscle of the rectum of Wistar-ST rats

Participation of the nitric oxide-cyclic GMP pathway in nonadrenergic, nonc holinergic (NANC) relaxation induced by electrical field stimulation of lon gitudinal muscle of the rectum of Wistar-ST rats was studied by using a sel ective inhibitor of soluble guanylyl cyclase, 1H-[1,2,4]oxadiazolo[4,3-a]qu inoxalin-1-one (ODQ), ODQ concentration dependently inhibited the relaxatio n and at 10 mu M, maximally inhibited it by 83%. However, results obtained with N-G-nitro-L-arginine, L-arginine and exogenously added nitric oxide ex cluded the participation of nitric oxide in the relaxation. An inhibitor of cyclic CMP-dependent protein kinase (PKG) partially (39%) inhibited the re laxation. ODQ also significantly inhibited the relaxation, which persisted after the PKC inhibitor-treatment, by 85%. The results strongly suggest tha t ODQ inhibits the NANC relaxation in a cyclic GMP-PKG pathway-independent manner.