The compound BAY 41-2272 stimulates the soluble guanylyl cyclase in a nitric oxide (NO)-independent manner. We have investigated the potency and efficacy of BAY 41-2272 in the rat anococcygeus muscle, as well as the effects of BAY 41-2272 on NO-mediated anococcygeus relaxations. BAY 41-2272 (0.01-10 mu M) potently relaxed precontracted anococcygeus muscle strips, with a pEC(50) value of 6.44 +/- 0.03 and maximum response of 100 +/- 2%. The soluble guanylyl cyclase inhibitor H-1-[1,2,4]-oxidiazolo[4,3-a] quinoxalin-1-one (ODQ, 1 mu M) and the NO inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME, 100 mu M) caused significant rightward shifts in the concentration-response curves to BAY 41-2272. The phosphodiesterase type-5 inhibitor tadalafil (0.1 mu M) markedly enhanced the relaxations evoked by BAY 41-2272. In addition, BAY 41-2272 increased the duration of nitrergic relaxations by approximately 55%. The relaxations induced by glyceryl trinitrate were also significantly potentiated by BAY 41-2272. In conclusion, BAY 41-2272 interacts with endogenous and exogenous NO causing a potent relaxation of rat anococcygeus muscle. (c) 2005 Elsevier B.V. All rights reserved.53041671157165