Portal de Periódicos da CAPES

Artigo Acesso aberto Produção Nacional Revisado por pares

BIBTEX RIS

Relaxant effect of a metal-based drug in human corpora cavernosa and its mechanism of action

2015; Springer Nature; Volume: 28; Issue: 1 Linguagem: Inglês

10.1038/ijir.2015.27

1476-5489

Alexandre S Leitão, Rafael Campos, João Batista Gadelha de Cerqueira, Manassés Claudino Fonteles, ⁠Cláudia Ferreira Santos, Gilberto De Nucci, Eduardo H. S. Sousa, Luiz Gonzaga de França Lopes, Lúcio Flávio Gonzaga-Silva, Nilberto Robson Falcão do Nascimento,

Sexual function and dysfunction studies

We studied the mechanisms involved in the human corpora cavernosa (HCC) relaxation induced by a new metal-based nitric oxide (NO) donor, the ruthenium complex cis-[Ru(bpy)2Imn(NO)](+3) (FOR0811). FOR0811 produced relaxation in phenylephrine (PE)-precontracted HCC with a maximal response that achieved 112.9 ± 10.6%. There was no difference between the maximal relaxation induced by FOR0811 when compared with sodium nitroprusside (SNP) (106.8 ± 7.3%), BAY41-2272 (107.6 ± 4.1%) or vardenafil (103.4 ± 3.8%), however, FOR0811 was less potent than SNP and vardenafil. L-N(G)-nitroarginine methyl ester (L-NAME), a NO synthase inhibitor, had no effect in the concentration-response curve elicited by FOR0811. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a heme-site inhibitor of soluble guanylyl cyclase (sGC) was able to either block or reverse the relaxation induced by FOR0811. On the other hand, the relaxation induced by FOR0811 was not affected by glibenclamide, a blocker of ATP-sensitive potassium channels. FOR0811 (10 μM) was able to increase cyclic guanosine monophosphate (cGMP) levels in corpora cavernosa strips. FOR0811 completely relaxes HCC by a sGC-cGMP-dependent mechanism and can be a lead compound in the development of new stable NO donors.