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 microM) 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 1H-[1,2,4]-oxidiazolo[4,3-a] quinoxalin-1-one (ODQ, 1 microM) and the NO inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 microM) caused significant rightward shifts in the concentration-response curves to BAY 41-2272. The phosphodiesterase type-5 inhibitor tadalafil (0.1 microM) 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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Carbachol / pharmacology
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Carbolines / pharmacology
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Colforsin / pharmacology
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Cyclic AMP / metabolism
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Cyclic GMP / metabolism
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Dose-Response Relationship, Drug
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Drug Synergism
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Electric Stimulation
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Enzyme Activation / drug effects
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Enzyme Inhibitors / pharmacology
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Guanylate Cyclase
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Muscle Contraction / drug effects
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Muscle Relaxation / drug effects*
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Muscle, Smooth / drug effects*
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Muscle, Smooth / physiology
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NG-Nitroarginine Methyl Ester / pharmacology
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Nitric Oxide / pharmacology*
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Nitric Oxide Donors / pharmacology
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Nitric Oxide Synthase / antagonists & inhibitors
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Nitric Oxide Synthase / metabolism
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Nitroglycerin / pharmacology
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Oxadiazoles / pharmacology
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Pyrazoles / pharmacology*
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Pyridines / pharmacology*
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Quinoxalines / pharmacology
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Rats
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Rats, Wistar
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Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors
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Receptors, Cytoplasmic and Nuclear / metabolism*
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Soluble Guanylyl Cyclase
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Tadalafil
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Tetrodotoxin / pharmacology
Substances
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1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one
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3-(4-Amino-5-cyclopropylpyrimidine-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo(3,4-b)pyridine
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Carbolines
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Enzyme Inhibitors
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Nitric Oxide Donors
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Oxadiazoles
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Pyrazoles
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Pyridines
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Quinoxalines
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Receptors, Cytoplasmic and Nuclear
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Colforsin
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Nitric Oxide
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Tetrodotoxin
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Tadalafil
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Carbachol
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Cyclic AMP
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Nitric Oxide Synthase
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Guanylate Cyclase
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Soluble Guanylyl Cyclase
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Nitroglycerin
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Cyclic GMP
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NG-Nitroarginine Methyl Ester