Relaxing effects induced by the soluble guanylyl cyclase stimulator BAY 41-2272 in human and rabbit corpus cavernosum

• Published in: European journal of pharmacology Vol. 477; no. 2; pp. 163 - 169
• Main Authors: Baracat, Juliana S., Teixeira, Cleber E., Okuyama, Cristina E., Priviero, Fernanda B.M., Faro, Renato, Antunes, Edson, De Nucci, Gilberto
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 12.09.2003; Elsevier
• Subjects: Adolescent; Adult; Aged; Animals; BAY 41-2272; Biological and medical sciences; Corpus cavernosum; Cyclic AMP - metabolism; Drug Synergism; Enzyme Activators - pharmacology; Genital system. Reproduction; Guanylate Cyclase - antagonists & inhibitors; Guanylate Cyclase - metabolism; Humans; In Vitro Techniques; Isometric Contraction - drug effects; Male; Medical sciences; Middle Aged; Muscle Relaxation - drug effects; NG-Nitroarginine Methyl Ester - pharmacology; Nitric oxide (NO); Nitric Oxide - metabolism; Nitric Oxide Synthase - antagonists & inhibitors; Oxadiazoles - pharmacology; Penis - drug effects; Penis - physiology; Pharmacology. Drug treatments; Pyrazoles - pharmacology; Pyridines - pharmacology; Rabbits; Sildenafil; Soluble guanylyl cyclase; Corpus cavernosum; BAY 41-2272; Sildenafil; Soluble guanylyl cyclase; Nitric oxide (NO); Human; Vasodilator agent; Enzyme; Erection; Phosphorus-oxygen lyases; Rabbit; Lyases; Lagomorpha; Guanylate cyclase; In vitro; Vertebrata; Mammalia; Animal; Nitric oxide
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2003.08.012

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.