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Int J Impot Res ; 28(1): 20-4, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26510967

RESUMEN

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.


Asunto(s)
Guanilato Ciclasa/fisiología , Relajación Muscular , Donantes de Óxido Nítrico/farmacología , Erección Peniana , Pene , Receptores Citoplasmáticos y Nucleares/fisiología , Compuestos de Rutenio/farmacología , GMP Cíclico/fisiología , Humanos , Masculino , Relajación Muscular/efectos de los fármacos , Relajación Muscular/fisiología , Músculo Liso/efectos de los fármacos , Músculo Liso/fisiología , Óxido Nítrico/metabolismo , Nitroprusiato/farmacología , Erección Peniana/efectos de los fármacos , Erección Peniana/fisiología , Pene/patología , Pene/fisiología , Pene/fisiopatología , Proyectos de Investigación , Guanilil Ciclasa Soluble
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