Relaxing effects induced by the soluble guanylyl cyclase stimulator BAY 41-2272 in human and rabbit corpus cavernosum
| Autor: | Fernanda B.M. Priviero, Cristina E. Okuyama, Renato Faro, Edson Antunes, Cleber E. Teixeira, Gilberto De Nucci, Juliana S. Baracat |
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| Rok vydání: | 2003 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent Sildenafil Pyridines Muscle Relaxation Enzyme Activators Endogeny In Vitro Techniques Nitric Oxide Nitric oxide chemistry.chemical_compound Internal medicine Isometric Contraction medicine Cyclic AMP Animals Humans Aged Pharmacology chemistry.chemical_classification Oxadiazoles Lagomorpha biology Drug Synergism Middle Aged biology.organism_classification In vitro Endocrinology Enzyme NG-Nitroarginine Methyl Ester chemistry Guanylate Cyclase Pyrazoles Rabbits Nitric Oxide Synthase Soluble guanylyl cyclase Bay Penis |
| Zdroj: | European journal of pharmacology. 477(2) |
| ISSN: | 0014-2999 |
| Popis: | 5-Cyclopropyl-2-[1-(2-fluoro-benzyl)-1 H -pyrazolo[3,4- b ]pyridin-3-yl]-pyrimidin-4-ylamine (BAY 41-2272) is a potent soluble guanylyl cyclase stimulator in a nitric oxide (NO)-independent manner. The relaxant effect of BAY 41-2272 was investigated in rabbit and human corpus cavernosum in vitro. BAY 41-2272 (0.01–10 μM) relaxed both rabbit (pEC 50 =6.82±0.06) and human (pEC 50 =6.12±0.10) precontracted cavernosal strips. The guanylyl cyclase inhibitor (ODQ, 10 μM) caused significant rightward shifts in the concentration–response curves for BAY 41-2272 in rabbit (4.7-fold) and human (2.3-fold) tissues. The NO synthesis inhibitor ( N -nitro- l -arginine methyl ester ( l -NAME), 100 μM) also produced similar rightward shifts, revealing that BAY 41-2272 acts synergistically with endogenous NO to elicit its relaxant effect. The results also indicate that ODQ is selective for the NO-stimulated enzyme, since relaxations evoked by BAY 41-2272 were only partly attenuated by ODQ. The present study shows that both BAY 41-2272 and sildenafil evoke relaxations independent of inhibition of haem in soluble guanylate cyclase. Moreover, there is no synergistic effect of the two compounds in corpus cavernosum. |
| Databáze: | OpenAIRE |
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