Abstract6‐Nitrodopamine (6‐ND) is the main catecholamine released from human isolated vas deferens and the adrenergic nervous system is known to play a major role in the contractions of the epididymal portion of the vas deferens. Here it was investigated the interactions of 6‐ND on the contractions of the human isolated vas deferens induced by either classical catecholamines or electric‐field stimulation (EFS). The vas deferens obtained from 106 patients who underwent vasectomy surgery were mounted in a 10‐mL glass chamber filled with warmed (37°C) and oxygenated Krebs–Henseleit's solution. The strips were pretreated (30 min) with 6‐ND (0.1–100 nM) and exposed to increasing concentrations of noradrenaline (0.01–300 M), dopamine (0.00001–10 mM), or adrenaline (0.01–300 M). The strips were also submitted to EFS in tissues pre‐incubated or not with 6‐ND (1–100 nM), noradrenaline (100 nM), adrenaline (100 nM), or dopamine (100 nM). Catecholamine basal release was evaluated by LC–MS/MS and expression of tyrosine hydroxylase by both immunohistochemistry (IC) and fluorescence in‐situ hybridization (FISH). Pre‐incubation of the vas deferens with 6‐ND caused marked potentiation of the contractions induced by noradrenaline, adrenaline, and dopamine, as characterized by significant increases in Emax, without changes in pEC50 values. 6‐nitrodopamine also caused significant increases in the EFS‐induced contractions. The basal release of 6‐ND was not affected by pre‐treatment of the tissues with tetrodotoxin. Tyrosine hydroxylase was detected in epithelial cells of human vas deferens samples by both IC and FISH. The results clearly demonstrate that epithelium‐derived 6‐ND is a major modulator of human vas deferens contractility.
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