6-Nitrodopamine is released by human umbilical cord vessels and modulates vascular reactivity

Britto-Júnior, José; Silva, Weverton Castro Coelho; Murari, Guilherme Figueiredo; Nash, Charles Elliot Serpellone; Mónica, Fabíola Z.; Antunes, Edson; Nucci, Gilberto De

doi:10.1016/j.lfs.2021.119425

Cited by 27 publications

(35 citation statements)

References 26 publications

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“…The release of 6‐ND was reduced by pretreatment of the vas deferens with L‐NAME, indicating that the synthesis/release of 6‐ND is coupled to NO synthesis. Pretreatment of human umbilical cord vessels 5 and rat vas deferens 3 with L‐NAME is accompanied by decrease of 6‐ND synthesis/release. Chronic treatment of rats with L‐NAME also decreases the 6‐ND release by vas deferens 3 .…”

Section: Discussionmentioning

confidence: 97%

“…shown to be released from rat isolated vas deferens 3 and atria 4 and from human umbilical cord vessels. 5 The synthesis/release of 6nitrodopamine is reduced (but not abolished) when these tissues are incubated with the nitric oxide (NO) synthase inhibitor L-NAME. 6nitrodopamine can ben synthesized in vitro by incubation dopamine with nitric acid, 6 which generates NO or peroxynitrite.…”

Section: Introductionmentioning

confidence: 99%

“…Contractions of the vas deferens also have an important role in the propulsion of the spermatozoa and occur near‐simultaneously with the contractions of the seminal glands 2 . 6‐nitrodopamine (6‐ND) is a new catecholamine that has been recently shown to be released from rat isolated vas deferens 3 and atria 4 and from human umbilical cord vessels 5 . The synthesis/release of 6‐nitrodopamine is reduced (but not abolished) when these tissues are incubated with the nitric oxide (NO) synthase inhibitor L‐NAME.…”

Section: Introductionmentioning

confidence: 99%

“…Whether this process in vivo is a chemical, or enzymatic process is yet to be determined. Since 6‐nitrodopamine is a potent vasodilator, 5,7 the formation of this novel catecholamine rather than stimulation of soluble guanlylate cyclase 8 may be an important mechanism of action for NO. The contractions caused by 6‐ND in the rat isolated vas deferens are selectively antagonized by tricyclic antidepressants such as amitriptyline, desipramine and clomipramine 3 and by α 1 ‐adrenergic receptor blockers such as doxazosin, tamsulosin and silodosin 9 …”

Section: Introductionmentioning

confidence: 99%

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6‐nitrodopamine is a major endogenous modulator of human vas deferens contractility

et al. 2022

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Background Rat isolated vas deferens releases 6‐nitrodopamine (6‐ND), and the spasmogenic activity of this novel catecholamine is significantly reduced by tricyclic compounds such as amitriptyline, desipramine, and carbamazepine and by antagonists of the α1‐adrenergic receptors such as doxazosin, tamsulosin, and prazosin. Objectives To investigate the liberation of 6‐ND by human epididymal vas deferens (HEVDs) and its pharmacological actions. Methods The in vitro liberation of 6‐ND, dopamine, noradrenaline, and adrenaline from human vas deferens was evaluated by LC‐MS/MS. The contractile effect of the catecholamines in HEVDs was investigated in vitro. The action of tricyclic antidepressants was evaluated on the spasmogenic activity ellicited by the catecholamines and by the electric‐field stimulation (EFS). The tissue was also incubated with the inhibitor of nitric oxide (NO) synthase L‐NAME and the release of catecholamines and the contractile response to EFS were assessed. Results 6‐ND is the major catecholamine released from human vas deferens and its synthesis/release is inhibited by NO inhibition. The spasmogenic activity elicited by EFS in the human vas deferens was blocked by tricyclic antidepressants only at concentrations that selectively antagonize 6‐ND induced contractions of the human vas deferens, without affecting the spasmogenic activity induced by dopamine, noradrenaline, and adrenaline in this tissue. Incubation of the vas deferens with L‐NAME reduced both the 6‐ND release and the contractions induced by EFS. Discussion and conclusion 6‐ND should be considered a major endogenous modulator of human vas deferens contractility and possibly plays a pivotal role in the emission process of ejaculation. It offers a novel and shared mechanism of action for tricyclic antidepressants and α1‐adrenergic receptor antagonists.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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6‐nitrodopamine is a major endogenous modulator of human vas deferens contractility

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“…6-Nitrodopamine (6-ND) is a novel catecholamine that is released by the endothelium of human cord vessels ( 4 ), Chelonoidis carbonarius aortic rings ( 5 ), and Pantherophis guttatus aortic rings ( 6 ). In these vascular tissues, 6-ND is a potent vasodilator, acting as a highly selective dopamine D 2 -like receptor antagonist.…”

Section: Introductionmentioning

confidence: 99%

Relaxation of thoracic aorta and pulmonary artery rings of marmosets (Callithrix spp.) by endothelium-derived 6-nitrodopamine

Britto

Lima

Santos-Xavier

et al. 2023

Braz J Med Biol Res

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6-Nitrodopamine is a novel catecholamine released by vascular tissues, heart, and vas deferens. The aim of this study was to investigate whether 6-nitrodopamine is released from the thoracic aorta and pulmonary artery rings of marmosets ( Callithrix spp. ) and to evaluate the relaxing and anti-contractile actions of this catecholamine. Release of 6-nitrodopamine, dopamine, noradrenaline, and adrenaline was assessed by liquid chromatography with tandem mass spectrometry (LC-MS/MS). The relaxations induced by 6-nitrodopamine and by the selective dopamine D2 receptor antagonist L-741,626 were evaluated on U-46619 (3 nM)-pre-contracted vessels. The effects of 6-nitrodopamine and L-741,626 on the contractions induced by electric-field stimulation (EFS), dopamine, noradrenaline, and adrenaline were also investigated. Both aorta and pulmonary artery rings exhibited endothelium-dependent release of 6-nitrodopamine, which was significantly reduced by the NO synthesis inhibitor L-NAME. Addition of 6-nitrodopamine or L-741,626 caused concentration-dependent relaxations of both vascular tissues, which were almost abolished by endothelium removal, whereas L-NAME and the soluble guanylate cyclase inhibitor ODQ had no effect on 6-nitrodopamine-induced relaxations. Additionally, pre-incubation with 6-nitrodopamine antagonized the dopamine-induced contractions, without affecting the noradrenaline- and adrenaline-induced contractions. Pre-incubation with L-741,626 antagonized the contractions induced by all catecholamines. The EFS-induced contractions were significantly increased by L-NAME, but unaffected by ODQ. Immunohistochemical assays showed no immunostaining of the neural tissue markers S-100 and calretinin in either vascular tissue. The results indicated that 6-nitrodopamine is the major catecholamine released by marmoset vascular tissues, and it acts as a potent and selective antagonist of dopamine D 2 -like receptors. 6-nitrodopamine release may be the major mechanism by which NO causes vasodilatation.

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Measurement of 6‐cyanodopamine, 6‐nitrodopa, 6‐nitrodopamine and 6‐nitroadrenaline by LC–MS/MS in Krebs–Henseleit solution. Assessment of basal release from rabbit isolated right atrium and ventricles

Júnior,

Britto‐Júnior,

Magalhaes

et al. 2023

Biomedical Chromatography

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This study presents the validation of a sensitive method for the determination of 6‐nitrodopa, 6‐nitrodopamine, 6‐nitroadrenaline and 6‐cyanodopamine in Krebs–Henseleit solution by LC–MS/MS with ESI+. HRMS was used to precisely characterize the structures of the fragment ions. The method was applied to investigate the catecholamine basal release from rabbit isolated atria and ventricles. The atria and ventricles were suspended separately in a 5 ml organ bath containing Krebs–Henseleit solution with ascorbic acid (3 mM), gassed (95%O2/5%CO2) at 37°C for 30 min. Strata‐X 33 μm SPE cartridges were employed for the extraction of the catecholamines and the internal standard 6‐nitrodopamine‐d4. The catecholamines were separated employing a 150 × 3 mm Shim‐pack GIST C18‐AQ (3 mm particle size), placed in an oven at 40°C and perfused by 65% of mobile phase A (MeCN/H2O; 90/10, v/v) + 0.4% CH3COOH and 35% mobile phase B (deionized H2O) + 0.2% CH2O2 at 320 μl/min in isocratic mode. The method was linear at 0.1–20 ng/ml. The method was used to identify for the first‐time basal release of the three nitrocatecholamines mentioned above and a member of a novel class of catecholamines, the cyanocatecholamines.

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6-Nitrodopamine is released by human umbilical cord vessels and modulates vascular reactivity

Cited by 27 publications

References 26 publications

6‐nitrodopamine is a major endogenous modulator of human vas deferens contractility

6‐nitrodopamine is a major endogenous modulator of human vas deferens contractility

Relaxation of thoracic aorta and pulmonary artery rings of marmosets (Callithrix spp.) by endothelium-derived 6-nitrodopamine

Measurement of 6‐cyanodopamine, 6‐nitrodopa, 6‐nitrodopamine and 6‐nitroadrenaline by LC–MS/MS in Krebs–Henseleit solution. Assessment of basal release from rabbit isolated right atrium and ventricles

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