Investigation on the positive chronotropic action of 6-nitrodopamine in the rat isolated atria

Britto-Júnior, José; Lima, Antonio Tiago; Fuguhara, Vivian; Mónica, Fabíola Z.; Antunes, Edson; Nucci, Gilberto De

doi:10.1007/s00210-023-02394-9

Cited by 13 publications

(9 citation statements)

References 47 publications

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“…Besides being a potent modulator of heart chronotropism (Britto‐Júnior, de Oliveira, et al, 2022; Britto‐Júnior, Lima, Fuguhara, et al, 2023) and inotropism (Britto‐Júnior, Medeiros‐Teixeira, et al, 2023), 6‐nitrodopamine also modulates rat (Britto‐Júnior, Lima, Campos, et al, 2023; Britto‐Júnior, Ribeiro, et al, 2022; Britto‐Júnior, Ximenes, et al, 2021; Lima, Amorim, et al, 2022) and human (Britto‐Júnior, da Silva‐Filho, et al, 2022) vas deferens differently. The evaluation of the biological activity of this novel class of catecholamines, and the different patterns of release observed in atria and ventricles, should deepen our understanding of cardiovascular physiology and pathology.…”

Section: Discussionmentioning

confidence: 99%

“…6‐ND is also released from rat both isolated right atrium (Britto‐Júnior, de Oliveira, et al, 2022) and ventricles (Britto‐Júnior, Medeiros‐Teixeira, et al, 2023). In the atrium it behaves as a positive chronotropic agent, being 100 times more potent than noradrenaline and adrenaline (Britto‐Júnior, de Oliveira, et al, 2022; Britto‐Júnior, Lima, Fuguhara, et al, 2023). In the Langendorff preparation of the rat isolated heart (Britto‐Júnior, Medeiros‐Teixeira, et al, 2023), 6‐ND acts as a positive and potent inotropic agent.…”

Section: Introductionmentioning

confidence: 99%

“…In the Langendorff preparation of the rat isolated heart (Britto‐Júnior, Medeiros‐Teixeira, et al, 2023), 6‐ND acts as a positive and potent inotropic agent. 6‐ND is a catecholamine that in the heart is not originated from the nerve terminals, since its release is not affected by incubating either the atria or ventricles with tetrodotoxin (Britto‐Júnior, de Oliveira, et al, 2022; Britto‐Júnior, Lima, Fuguhara, et al, 2023). The release of 6‐ND from either vascular tissues or the heart is reduced when the tissues are pre‐incubated with the nitric oxide (NO) synthase inhibitor l ‐NAME (Boer et al, 2000; Rees et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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“…In addition, in the rat isolated right atrium, 6-ND exerts a positive chronotropic effect being one 100 times more potent than noradrenaline and adrenaline, and 10.000 times more potent than dopamine (Britto-Júnior et al, 2022d). 6-ND also strongly potentiates the positive chronotropic effects induced by noradrenaline, adrenaline and dopamine (Britto-Júnior et al, 2023b). This potentiation was inhibited by incubating the atrium with the voltage-gated sodium channel blocker tetrodotoxin (Narahashi et al, 1967) or when the atrium was obtained from animals pre-treated with reserpine, indicating that 6-ND causes release of catecholamines from adrenergic terminals.…”

Section: Introductionmentioning

confidence: 89%

6-Nitrodopamine potentiates contractions of rat isolated vas deferens induced by noradrenaline, adrenaline, dopamine and electric field stimulation

Britto-Júnior

Lima

Campos

et al. 2023

Naunyn-Schmiedeberg's Arch Pharmacol

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6-nitrodopamine (6-ND) is a novel endogenous catecholamine that is released from rat isolated vas deferens, and it has been characterized as a major modulator of the contractility of rat isolated epididymal vas deferens (RIEVD). Drugs such as tricyclic antidepressants, a 1 and b 1 b 2 adrenoceptor blockers, act as selective antagonists of the 6-ND receptor in the RIEVD. In the rat isolated atria, 6-ND has a potent positive chronotropic action and causes remarkable potentiation of the positive chronotropic effects induced by dopamine, noradrenaline, and adrenaline. Here it was investigated whether 6-ND interacts with the classical catecholamines in the rat isolated vas deferens.Incubation with 6-ND (0.1 and 1nM; 30min) caused no contractions in the RIEVD but provoked signi cant leftward shifts in the concentration-response curves to noradrenaline, adrenaline, and dopamine. Preincubation of the RIEVD with 6-ND (1nM), potentiated the contractions induced by electric-eld stimulation (EFS), whereas pre-incubation with 1nM of dopamine, noradrenaline or adrenaline, did not affect EFS-induced contractions. In tetrodotoxin (1mM) pre-treated (30 min) RIEVD, pre-incubation with 6-ND (0.1nM) did not caused leftward shifts in the concentration-dependent contractions induced by noradrenaline, adrenaline, or dopamine. Pre-incubation of the RIEVD with the α 2A -adrenoceptor antagonist idazoxan (30 min, 10 nM) did not affect dopamine, noradrenaline, adrenaline, and EFS-induced contractions. However, when idazoxan (10nM) and 6-ND (0.1nM) were simultaneously pre-incubated (30 min), a signi cant potentiation of the EFS-induced contractions of the RIEVD was observed. 6nitrodopamine causes remarkable potentiation of dopamine, noradrenaline, and adrenaline contractions on the RIEVD, due to activation of adrenergic terminals, possibly via pre-synaptic adrenoceptors.

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“…In the isolated atria, the stimulation of b1-adrenoceptors is associated with increases in atrial rate (Brodde, 1991). Interestingly, the positive chronotropic effect induced by 6-ND is selectively blocked by β1-adrenoceptor antagonists such as atenolol, betaxolol and metoprolol at concentrations that do not affect the positive chronotropic effect induced by dopamine, noradrenaline, and adrenaline (Britto-Júnior et al, 2023b). Propranolol is a member of the 3-(aryloxy)-1-(alkylamino)-β-blocker family, a class of drugs where the activity is restricted mainly to the S-isomer (Welson and Burke, 1978), and is classified as a non-selective, surmountable, b-blocker (Coltart et., 1975).…”

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confidence: 99%

4-Nitro-propranolol selectively inhibits the positive chronotropic effect induced by 6-nitrodopamine in the rat isolated right atrium

Oliveira,

Cardoso,

Britto-Júnior

et al. 2023

Preprint

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6-Nitrodopamine (6-ND) is released from isolated atria of rabbit, rat and mice and has significant positive chronotropic action. The positive chronotropic effect induced by 6-ND is selectively blocked by β1-adrenoceptor antagonists at concentrations that do not affect the positive chronotropic effect induced by dopamine, noradrenaline, and adrenaline. Here the effects of propranolol, 4-NO2-propranolol and 7-NO2-propranolol were investigated in the rat isolated right atrium. The right atrium was mounted between two metal hooks in 10-mL custom designed glass chambers containing Krebs-Henseleit’s solution, continuously gassed (95%O2:5%CO2) and heated (37°C). Tissues were allowed to equilibrate under a resting tension of 10 mN for one hour, and the isometric tension was registered using a PowerLab system. 4-NO2-propranol was more potent than propranolol as a negative chronotropic agent. At 30 nM, 4-NO2-propranolol did not affect the chronotropic effect of dopamine, noradrenaline, and adrenaline. The S-isomer of 4- NO2-propranolol, but not the R-isomer, was active. Propranolol induced fall in atrial rate at concentrations higher than those required to block the chronotropic effects of dopamine, noradrenaline and adrenaline, but enough to block the 6-ND effect. 7-NO2-propranolol was only active at very high concentration, and the effect was not stereoselective. The negative chronotropic effects induced by 4-NO2-propranolol (100 nM) and propranolol (300 nM) were not observed in L-NAME treated atria, whereas that induced by 7-NO2-propranolol (10 mM) was unaffected. The potent and selective inhibition observed with (±)-4-NO2-propranolol reinforces the concept that 6-ND is a major mediator of heart chronotropism and the main target of the so-called b-blockers.

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Investigation on the positive chronotropic action of 6-nitrodopamine in the rat isolated atria

Cited by 13 publications

References 47 publications

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

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 potentiates contractions of rat isolated vas deferens induced by noradrenaline, adrenaline, dopamine and electric field stimulation

4-Nitro-propranolol selectively inhibits the positive chronotropic effect induced by 6-nitrodopamine in the rat isolated right atrium

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