TY - JOUR
T1 - Stimulation of soluble guanylyl cyclase by BAY 41-2272 relaxes anococcygeus muscle
T2 - Interaction with nitric oxide
AU - Teixeira, Cleber E.
AU - Priviero, Fernanda B.M.
AU - Claudino, Mário A.
AU - Baracat, Juliana S.
AU - De Nucci, Gilberto
AU - Webb, R. Clinton
AU - Antunes, Edson
PY - 2006/1/13
Y1 - 2006/1/13
N2 - 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 μM) potently relaxed precontracted anococcygeus muscle strips, with a pEC50 value of 6.44 ± 0.03 and maximum response of 100 ± 2%. The soluble guanylyl cyclase inhibitor 1H-[1,2,4]-oxidiazolo[4,3-a] quinoxalin-1-one (ODQ, 1 μM) and the NO inhibitor Nω-nitro- l-arginine methyl ester (l-NAME, 100 μM) caused significant rightward shifts in the concentration-response curves to BAY 41-2272. The phosphodiesterase type-5 inhibitor tadalafil (0.1 μM) 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.
AB - 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 μM) potently relaxed precontracted anococcygeus muscle strips, with a pEC50 value of 6.44 ± 0.03 and maximum response of 100 ± 2%. The soluble guanylyl cyclase inhibitor 1H-[1,2,4]-oxidiazolo[4,3-a] quinoxalin-1-one (ODQ, 1 μM) and the NO inhibitor Nω-nitro- l-arginine methyl ester (l-NAME, 100 μM) caused significant rightward shifts in the concentration-response curves to BAY 41-2272. The phosphodiesterase type-5 inhibitor tadalafil (0.1 μM) 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.
KW - Anococcygeus muscle
KW - BAY 41-2272
KW - Nitrergic nerve
KW - Nitric oxide
KW - Soluble guanylyl cyclase
KW - Tadalafil
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U2 - 10.1016/j.ejphar.2005.11.015
DO - 10.1016/j.ejphar.2005.11.015
M3 - Article
C2 - 16371226
AN - SCOPUS:29844433446
VL - 530
SP - 157
EP - 165
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 1-2
ER -