beta(1)- and beta(1)/beta(2)-adrenergic receptor antagonists block 6-nitrodopamine-induced contractions of the rat isolated epididymal vas deferens

Autor(es)

Lima, Antonio Tiago ; Amorim, Amanda Consulin ; Britto-Junior, Jose ; Campitelli, Raquel Rios ; Fregonesi, Adriano ; Monica, Fabiola Z. ; Antunes, Edson ; De Nucci, Gilberto

• Tipo de documento: Artigo Científico
• Fonte: NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY; v. 395, n. 10, p. 12-pg., 2022-07-08.

Resumo

6-Nitrodopamine (6-ND) is an endogenous modulator of the contractility in the rat isolated epididymal vas deferens (RIEVD) and considered to be the main peripheral mediator of the emission process. Use of selective and unselective beta-adrenergic receptor antagonists has been associated with ejaculatory failure. Here, the effects of selective beta(1)- and beta(1)/beta(2)-adrenergic receptor antagonists on RIEVD contractions induced by 6-ND, dopamine, noradrenaline, adrenaline, and electric-field stimulation (EFS) were investigated. The selective beta(1)-adrenergic receptor antagonists atenolol (0.1 and 1 mu M), betaxolol (1 mu M), and metoprolol (1 mu M) and the unselective beta(1)/beta(2)-adrenergic receptor antagonists propranolol (1 and 10 mu M) and pindolol (10 mu M) caused significant rightward shifts of the concentration-response curve to 6-ND (pA(2) 6.41, 6.91, 6.75, 6.47, and 5.74; for atenolol, betaxolol, metoprolol, propranolol, and pindolol), but had no effect on dopamine-, noradrenaline-, and adrenaline-induced contractions. The effects of selective beta(1)- and beta(1)/beta(2)-adrenergic receptor antagonists at a higher concentration (atenolol 1 mu M, betaxolol 1 mu M, metoprolol 1 mu M, propranolol 10 mu M, and pindolol 10 mu M) also reduced the EFS-induced RIEVD contractions in control, but not in RIEVD obtained from L-NAME-treated animals. The selective beta(1)-adrenoceptor agonist RO-363, the selective beta(2)-adrenoceptor agonist salbutamol, and the selective beta(3)-adrenoceptor agonist mirabegron, up to 300 mu M, had no effect on the RIEVD tone. The results demonstrate that beta(1)- and beta(1)-/beta(2)-adrenoceptor receptor antagonists act as 6-ND receptor antagonists in RIEVD, further confirming the main role of 6-ND in the RIEVD contractility. (AU)

• Processo FAPESP: 21/14120-4 - Avaliação dos antagonistas beta adrenérgicos no ducto de canal deferente em rato
• Beneficiário: Raquel Rios Campitelli
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• 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: 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: 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