Stimulation of soluble guanylyl cyclase by BAY 41-2272 relaxes anococcygeus muscle: Interaction with nitric oxide

Cleber E. Teixeira; Fernanda B.M. Priviero; Mário A. Claudino; Juliana S. Baracat; Gilberto De Nucci; R. Clinton Webb; Edson Antunes

doi:10.1016/j.ejphar.2005.11.015

Stimulation of soluble guanylyl cyclase by BAY 41-2272 relaxes anococcygeus muscle: Interaction with nitric oxide

Cleber E. Teixeira, Fernanda B.M. Priviero, Mário A. Claudino, Juliana S. Baracat, Gilberto De Nucci, R. Clinton Webb, Edson Antunes

Physiology

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10 Scopus citations

Abstract

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 N^ω-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.

Original language	English (US)
Pages (from-to)	157-165
Number of pages	9
Journal	European Journal of Pharmacology
Volume	530
Issue number	1-2
DOIs	https://doi.org/10.1016/j.ejphar.2005.11.015
State	Published - Jan 13 2006

Keywords

Anococcygeus muscle
BAY 41-2272
Nitrergic nerve
Nitric oxide
Soluble guanylyl cyclase
Tadalafil

ASJC Scopus subject areas

Pharmacology

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10.1016/j.ejphar.2005.11.015

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@article{ca71823dc808418b83e7073116c7ff5a,

title = "Stimulation of soluble guanylyl cyclase by BAY 41-2272 relaxes anococcygeus muscle: Interaction with nitric oxide",

abstract = "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.",

keywords = "Anococcygeus muscle, BAY 41-2272, Nitrergic nerve, Nitric oxide, Soluble guanylyl cyclase, Tadalafil",

author = "Teixeira, {Cleber E.} and Priviero, {Fernanda B.M.} and Claudino, {M{\'a}rio A.} and Baracat, {Juliana S.} and {De Nucci}, Gilberto and Webb, {R. Clinton} and Edson Antunes",

note = "Funding Information: The authors are grateful to Funda{\c c}{\~a}o de Amparo {\`a} Pesquisa do Estado de S{\~a}o Paulo (FAPESP) and to the American Heart Association (Southeast Affiliate) for providing financial support.",

year = "2006",

month = jan,

day = "13",

doi = "10.1016/j.ejphar.2005.11.015",

language = "English (US)",

volume = "530",

pages = "157--165",

journal = "European Journal of Pharmacology",

issn = "0014-2999",

publisher = "Elsevier",

number = "1-2",

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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

N1 - Funding Information: The authors are grateful to Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) and to the American Heart Association (Southeast Affiliate) for providing financial support.

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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UR - http://www.scopus.com/inward/citedby.url?scp=29844433446&partnerID=8YFLogxK

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 -

Stimulation of soluble guanylyl cyclase by BAY 41-2272 relaxes anococcygeus muscle: Interaction with nitric oxide

Abstract

Keywords

ASJC Scopus subject areas

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