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

Abstract

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.

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

“…6‐Nitrodopamine (6‐ND) is a novel catecholamine that is released by human umbilical cord vessels (Britto‐Júnior, Coelho‐Silva, et al, 2021), aortic rings in the tortoise Chelonoidis carbonaria (Britto‐Júnior, Campos, et al, 2022), in the snake Panterophis guttatus (Lima, Dos Santos, et al, 2022) and the marmoset Callithrix spp (Britto‐Júnior, Lima, Santos‐Xavier, et al, 2023). In the vasculature, 6‐ND causes vasodilation, acting as a truly selective dopamine D 2like ‐receptor antagonist (Britto‐Júnior, Coelho‐Silva, et al, 2021; Britto‐Júnior, Medeiros‐Teixeira, et al, 2023; Lima, Dos Santos, et al, 2022).…”

Endothelium-Derived Dopamine and 6-Nitrodopamine in the Cardiovascular System

“…Basal release of 6-nitrodopamine (6-ND), measured by HPLC positive electrospray tandem mass spectroscopy (HPLC-MS/MS), with a limit of quantitation of 100 pg/mL, was identified from the following vascular tissues in vitro: human umbilical artery and vein ( 34 ), human popliteal arterial and vein ( 35 ), tortoise aorta ( 36 ), corn snake aorta ( 37 ), and pulmonary artery and aorta obtained from the marmoset Callitrix s pp. ( 109 ). The basal release of 6-ND from the above vascular tissues was significantly reduced, but not abolished, when the vascular tissues were pretreated (30 min) with l -NAME and virtually abolished when the endothelial cells were taken away.…”

“…Adapted from Ref. 109 , with permission from Brazilian Journal of Medical and Biological Research , per Open Access terms.…”

GKT137831 and hydrogen peroxide increase the release of 6-nitrodopamine from the human umbilical artery, rat-isolated right atrium, and rat-isolated vas deferens

“…The basal release of dopamine (Britto-Júnior et al, 2020) and 6-nitrodopamine (6-ND; Britto-Júnior et al, 2021a) has been initially described from the human umbilical artery (HUA) but later identified also from other vascular tissues, such as the aortic rings of Chelonoidis carbonarius (Britto-Júnior et al, 2022a), Pantherophis guttatus (Lima et al, 2022), and Callithrix spp. (Britto-Júnior et al, 2023a) and in non-vascular tissues, such as rat-isolated atria (Britto-Júnior et al, 2022b) and rat- (Britto-Júnior et al, 2021b) and human-isolated vas deferens (Britto-Júnior et al, 2022c). In the cardiovascular system, 6-ND acts as a potent vasodilator and presents both positive chronotropic and inotropic effects (Zatz and De Nucci, 2023).…”