| Texto completo | |
| Autor(es): |
de Oliveira, Mariana Goncalves
;
Britto-Junior, Jose
;
Dias, Douglas Rafael Martins
;
Pereira, Luise Gabriela Santos
;
Chiavegatto, Silvana
;
Hermawan, Idam
;
Shimokawa, Hiroaki
;
Tsutsui, Masato
;
Antunes, Edson
;
De Nucci, Gilberto
Número total de Autores: 10
|
| Tipo de documento: | Artigo Científico |
| Fonte: | NITRIC OXIDE-BIOLOGY AND CHEMISTRY; v. 153, p. 8-pg., 2024-10-29. |
| Resumo | |
6-Nitrodopamine (6-ND) modulates vas deferens, seminal vesicles, and corpus cavernosum contractility; however, its role on the lower urinary tract organs has not been evaluated. Investigations of isolated urinary bladders from wild-type (WT) mice revealed 6-ND release was comparable to that of dopamine and adrenaline, whereas noradrenaline was hardly detected, as assessed by liquid chromatography coupled to tandem mass spectrometry. In vitro, 6-ND induced concentration-dependent relaxations in carbachol pre-contracted bladders with high potency (pEC50: 8.04 f 0.86), independently of eNOS/sGC activity. Co-incubation of 6-ND (1-10 mu M) antagonizes the contractile effects of acetylcholine (p < 0.05). Experiments using nitric oxide synthase (NOS) knockout mice demonstrated that 6-ND release from isolated urinary bladder was significantly reduced by neuronal NOS (nNOS-/-) deletion and abolished by triple NOSs deletion (n/i/eNOS-/-), while no significant changes were observed in endothelial (eNOS-/-) or inducible (iNOS-/-) knockout mice. Incubation with tetrodotoxin resulted in a significant decrease in 6-ND release in bladders obtained from WT, but not in nNOS- /- mice. The bladders from nNOS-/- and n/i/eNOS- /- mice exhibited significantly higher contractile responses to electric field stimulation (EFS), compared to eNOS- /-, iNOS-/-, or WT bladders. The hyperreactivity observed in triple NOS knockouts was reversed by the incubation with bladder mucosal layer obtained from a donor WT mice, but not with the muscular layer. These findings clearly demonstrate 6-ND is the most potent endogenous relaxing agent of urinary bladder, and inhibition of its release is associated with bladder hyperreactivity. (AU) | |
| Processo FAPESP: | 17/06100-8 - Suscetibilidade e resiliência aos efeitos do estresse psicossocial crônico na adolescência: estudo da participação da enzima neuronal de síntese do óxido nítrico (nNOS) |
| Beneficiário: | Silvana Chiavegatto |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 21/14414-8 - Avaliação da ação das nitro-catecolaminas no sistema cardiovascular |
| Beneficiário: | José Britto Júnior |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 23/09792-9 - Avaliação das Ações da 6-Nitrodopamina sobre a Função Renal e Geniturinária |
| Beneficiário: | Mariana Gonçalves de Oliveira Taranto |
| Modalidade de apoio: | Bolsas no Brasil - Programa Fixação de Jovens Doutores |
| Processo FAPESP: | 19/16805-4 - Avaliação do papel fisiopatológico das catecolaminas endoteliais |
| Beneficiário: | Gilberto de Nucci |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |