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

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Author(s):
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
Total Authors: 10
Document type: Journal article
Source: NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY; v. 397, n. 5, p. 12-pg., 2023-11-01.
Abstract

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)

FAPESP's process: 17/15175-1 - Modulation of soluble guanylate cyclase and the intracellular levels of cyclic nucleotides in the lower urinary tract and prostate
Grantee:Edson Antunes
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 19/16805-4 - Evaluation of the pathophysiological role of endothelial catecholamines
Grantee:Gilberto de Nucci
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 21/13593-6 - Evaluation of chronic 6-nitrodopamine treatment in rats
Grantee:Antonio Tiago Silva Lima
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 22/08022-2 - Evaluation of chronic treatment of 6-nitronoradrenaline in rats
Grantee:Gilberto Quirino dos Santos Junior
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 21/14414-8 - Evaluation of the action of nitro-catecholamines in the cardiovascular system
Grantee:José Britto Júnior
Support Opportunities: Scholarships in Brazil - Post-Doctoral