Alpha 1 -adrenergic blockers selectively antagonize the contractions induced by 6-nitrodopamine in the human vas deferens.

Autor: Britto-Júnior J; Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, 126 Tessália Vieira de Camargo St, Campinas, Sao Paulo, 13083-887, Brazil. josebrittojr@dac.unicamp.br., Guimarães RAB; Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, 126 Tessália Vieira de Camargo St, Campinas, Sao Paulo, 13083-887, Brazil., Oliveira DL; Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, 126 Tessália Vieira de Camargo St, Campinas, Sao Paulo, 13083-887, Brazil., Lima AT; Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, 126 Tessália Vieira de Camargo St, Campinas, Sao Paulo, 13083-887, Brazil., Quirino Junior G; Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, 126 Tessália Vieira de Camargo St, Campinas, Sao Paulo, 13083-887, Brazil., de Oliveira Stocco GA; Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, 126 Tessália Vieira de Camargo St, Campinas, Sao Paulo, 13083-887, Brazil., Salgado Uramoto EH; Department of Surgery, Faculty of Medicine of Jundiaí, Jundiaí, Brazil., Fregonesi A; Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, 126 Tessália Vieira de Camargo St, Campinas, Sao Paulo, 13083-887, Brazil.; Department of Surgery, Faculty of Medicine of Jundiaí, Jundiaí, Brazil., Antunes E; Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, 126 Tessália Vieira de Camargo St, Campinas, Sao Paulo, 13083-887, Brazil., De Nucci G; Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, 126 Tessália Vieira de Camargo St, Campinas, Sao Paulo, 13083-887, Brazil.; Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.; Metropolitan University of Santos, Santos, Brazil.
Jazyk: angličtina
Zdroj: Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2024 May; Vol. 397 (5), pp. 3227-3238. Date of Electronic Publication: 2023 Nov 01.
DOI: 10.1007/s00210-023-02805-x
Abstrakt: 6-Nitrodopamine (6-ND) is released from human vas deferens and plays a modulatory role in the male ejaculation. Therapeutical use of α 1 -adrenoceptor antagonists is associated with ejaculatory abnormalities. To evaluate the effect of α 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 μM) 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 α 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 α 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.
(© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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