TY - JOUR
T1 - Relaxing effects induced by the soluble guanylyl cyclase stimulator BAY 41-2272 in human and rabbit corpus cavernosum
AU - Baracat, Juliana S.
AU - Teixeira, Cleber E.
AU - Okuyama, Cristina E.
AU - Priviero, Fernanda B.M.
AU - Faro, Renato
AU - Antunes, Edson
AU - De Nucci, Gilberto
N1 - Funding Information:
The authors are grateful to Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) for providing financial support.
PY - 2003/9/12
Y1 - 2003/9/12
N2 - 5-Cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-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 (pEC50=6.82±0. 06) and human (pEC50=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.
AB - 5-Cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-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 (pEC50=6.82±0. 06) and human (pEC50=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.
KW - BAY 41-2272
KW - Corpus cavernosum
KW - Nitric oxide (NO)
KW - Sildenafil
KW - Soluble guanylyl cyclase
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U2 - 10.1016/j.ejphar.2003.08.012
DO - 10.1016/j.ejphar.2003.08.012
M3 - Article
C2 - 14519420
AN - SCOPUS:1642275487
SN - 0014-2999
VL - 477
SP - 163
EP - 169
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 2
ER -