| Texto completo | |
| Autor(es): |
Lima, Antonio Tiago
;
Britto-Junior, Jose
;
Moraes, Manoel Odorico
;
Moraes, Maria Elisabete A.
;
Fregonesi, Adriano
;
Monica, Fabiola Z.
;
Antunes, Edson
;
De Nucci, Gilberto
Número total de Autores: 8
|
| Tipo de documento: | Artigo Científico |
| Fonte: | ANDROLOGY; v. 12, n. 6, p. 10-pg., 2023-12-29. |
| Resumo | |
Background6-Nitrodopamine (6-ND) is a novel endogenous catecholamine that has a potent relaxant action on vascular smooth muscle in vitro.ObjectivesTo evaluate the basal release of 6-ND and noradrenaline from rabbit-isolated corpus cavernosum (RbCC) and its relaxing action on this tissue.MethodsRabbit corpus cavernosa were dissected and suspended in a 5-mL organ bath containing oxygenated Krebs-Henseleit's solution. 6-ND and noradrenaline release was quantified by liquid chromatography coupled to tandem mass spectrometry. The relaxant activity of 6-ND was assessed in RbCC strips pre-contracted with endothelin-1 (10 nM).ResultsRabbit corpus cavernosum presented basal release of both 6-ND (2.9 +/- 0.8 ng/mL, n = 12) and noradrenaline (1.7 +/- 1.3 ng/mL, n = 12). The 6-ND release was reduced by pre-treatment with N omega-nitro-l-arginine methyl ester (l-NAME) (100 mu M), whereas that of noradrenaline was unaffected. Tetrodotoxin (TTX, 1 mu M) abolished the noradrenaline release but had no effect on 6-ND release, indicating a non-neurogenic origin for 6-ND. 6-ND and the selective dopamine D2-agonist L-741,626 caused concentration-dependent RbCC relaxations (pEC50 of 11 +/- 0.15 and 11.15 +/- 0.28, respectively). Pre-treatment with either l-NAME or the soluble guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-on (ODQ) (100 mu M) caused a rightward shift of the concentration-response curve to 6-ND, without affecting the L-741,626 responses. In TTX (100 nM)-pre-treated preparations, neither l-NAME nor ODQ shifted the 6-ND concentration-response curve. Dopamine, noradrenaline, and adrenaline caused concentration-dependent RbCC contractions. Pre-incubation with 6-ND concentration-dependently inhibited the dopamine-induced contractions, without affecting those induced by either noradrenaline or adrenaline.Discussion and conclusion6-Nitrodopamine is the most potent endogenous relaxant agent in RbCC ever described and represents a novel mechanism by which NO causes corpus cavernosum smooth muscle relaxation. The finding that 6-ND acts as a truly selective dopamine D2-receptor antagonist indicates that the balance of dopamine and 6-ND release/synthesis may be the main mechanism that modulates corpus cavernosum smooth muscle tonus in vivo. (AU) | |
| 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: | 17/15175-1 - Modulação da guanilato ciclase solúvel e dos níveis intracelulares de nucleotídeos cíclicos em órgãos do trato urinário inferior e próstata |
| Beneficiário: | Edson Antunes |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 19/16805-4 - Avaliação do papel fisiopatológico das catecolaminas endoteliais |
| Beneficiário: | Gilberto de Nucci |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 21/13593-6 - Avaliação do tratamento crônico da 6-nitrodopamina em ratos |
| Beneficiário: | Antonio Tiago Silva Lima |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado Direto |