Alpha₁-adrenergic blockers selectively antagonize the contractions induced by 6-nitrodopamine in the human vas deferens

Autor(es)

Britto-Junior, Jose ; Guimaraes, Renan Arthur Bosio ; Oliveira, Denis Lima ; Lima, Antonio Tiago ; Quirino, Gilberto ; Stocco, Gabriel Augusto de Oliveira ; Uramoto, Edson Hiroshi Salgado ; Fregonesi, Adriano ; Antunes, Edson ; De Nucci, Gilberto

• Tipo de documento: Artigo Científico
• Fonte: NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY; v. 397, n. 5, p. 12-pg., 2023-11-01.

Resumo

6-Nitrodopamine (6-ND) is released from human vas deferens and plays a modulatory role in the male ejaculation. Therapeutical use of alpha(1)-adrenoceptor antagonists is associated with ejaculatory abnormalities. To evaluate the effect of alpha(1)-adrenoceptor antagonists on the contractions induced by 6-ND, dopamine, noradrenaline, and adrenaline in the human epididymal vas deferens (HEVD). HEVD strips were suspended in glass chambers containing heated and oxygenated Krebs-Henseleit's solution. Cumulative concentration-response curves to catecholamines (10 nM-300 mu M) were constructed in HEVD strips pre-incubated (30 min) with doxazosin (0.1-1 nM), tamsulosin (1-10 nM), prazosin (10-100 nM) and/or silodosin (0.1-10 nM). The effects of these alpha(1)-adrenoceptor antagonists were also evaluated in the electric-field stimulation (EFS, 2-32 Hz)-induced contractions. Doxazosin (0.1 nM) caused significant reductions in 6-ND-induced HEVD contractions without affecting the contractions induced by dopamine, noradrenaline, and adrenaline. Similar results were observed with tamsulosin (1 nM) and prazosin (10 nM). At these concentrations, these alpha(1)-adrenoceptor antagonists largely reduced the EFS-induced contractions. Silodosin (1 nM) caused concentration-dependent rightward shifts of the concentration-response curves to 6-ND but had no effect on the contractions induced by dopamine and adrenaline. Silodosin (0.1 nM) only inhibited the contractions induced by noradrenaline. Silodosin at 1 nM, but not at 0.1 nM, caused significant reductions in the EFS-induced contractions. The results reinforce the concept that 6-ND plays a major role in the human vas deferens contractility and indicate that the ejaculation disorders caused by doxazosin, tamsulosin, prazosin and silodosin cause in man, may be due to inhibition of the contractions induced by 6-ND rather than by the classical catecholamines dopamine, noradrenaline, and adrenaline. (AU)

• 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
• Processo FAPESP: 22/08022-2 - Avaliação do tratamento crônico da 6-nitronoradrenalina em rato
• Beneficiário: Gilberto Quirino dos Santos Junior
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• 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