Stimulation of soluble guanylyl cyclase by BAY 41-2272 relaxes anococcygeus muscle: interaction with nitric oxide.
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.
Teixeira
Cleber E
CE
Department of Pharmacology, Faculty of Medical Sciences, UNICAMP, Campinas (SP), Brazil.
Priviero
Fernanda B M
FB
Claudino
Mário A
MA
Baracat
Juliana S
JS
De Nucci
Gilberto
G
Webb
R Clinton
RC
Antunes
Edson
E
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002243:Carbolines / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004558:Electric Stimulation; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D005996:Nitroglycerin / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000071756:Soluble Guanylyl Cyclase; D000068581:Tadalafil; D013779:Tetrodotoxin / Q000494:pharmacology
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; C423582:3-(4-Amino-5-cyclopropylpyrimidine-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo(3,4-b)pyridine; D002243:Carbolines; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; D011720:Pyrazoles; D011725:Pyridines; D011810:Quinoxalines; D018160:Receptors, Cytoplasmic and Nuclear; D005576:Colforsin; D009569:Nitric Oxide; D013779:Tetrodotoxin; D000068581:Tadalafil; D002217:Carbachol; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D005996:Nitroglycerin; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester