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

Denis Lima Oliveira,

Vinicius Francisco Cardoso,

José Britto‐Júnior

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 27, 2023

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

Language: Английский

Endothelium-Derived Dopamine and 6-Nitrodopamine in the Cardiovascular System DOI Creative Commons
Roberto Zatz, Gilberto De Nucci

Physiology, Journal Year: 2023, Volume and Issue: 39(1), P. 44 - 59

Published: Oct. 24, 2023

The review deals with the release of endothelium-derived dopamine and 6-nitrodopamine (6-ND) its effects on isolated vascular tissues hearts. Basal both 6-ND is present in human umbilical cord vessels, popliteal nonhuman primate reptilia aortas. basal was significantly reduced when were treated

Language: Английский

Citations

16

6-Nitrodopamine Is the Most Potent Endogenous Positive Inotropic Agent in the Isolated Rat Heart DOI Creative Commons

José Britto‐Júnior,

Lincoln Medeiros-Teixeira,

Antonio Tiago Lima

et al.

Life, Journal Year: 2023, Volume and Issue: 13(10), P. 2012 - 2012

Published: Oct. 4, 2023

Background: 6-nitrodopamine released from rat isolated atria exerts positive chronotropic action, being more potent than noradrenaline, adrenaline, and dopamine. Here, we determined whether is ventricles (RIV) modulates heart inotropism. Methods: Catecholamines RIV were quantified by LC-MS/MS their effects on inotropism evaluated measuring left ventricular developed pressure (LVDP) in Langendorff’s preparation. Results: was the major catecholamine RIV. Incubation with L-NAME (100 µM), but not tetrodotoxin (1 caused a significant reduction basal release. release significantly reduced obtained chronically treated animals. (0.01 pmol) increases LVDP dP/dtmax, whereas dopamine noradrenaline required 10 pmol, adrenaline 100 to induce similar dP/dtmax. The infusion of atenolol (10 nM) blocked induced 6-ND pmol), without affecting nmol that nmol). Conclusions: ventricles. It 1000 times selectively atenolol, indicating main regulator

Language: Английский

Citations

11

6-Cyanodopamine as an endogenous modulator of heart chronotropism and inotropism DOI

José Britto‐Júnior,

Antonio Tiago Lima,

Denis Lima Oliveira

et al.

Life Sciences, Journal Year: 2025, Volume and Issue: unknown, P. 123504 - 123504

Published: Feb. 1, 2025

Language: Английский

Citations

0

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

José Britto‐Júnior,

Rafael Furlaneto,

Antonio Tiago Lima

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: April 5, 2024

Introduction: The human umbilical artery (HUA), rat-isolated right atrium, and vas deferens present a basal release of 6-nitrodopamine (6-ND). 6-ND from these tissues was significantly decreased (but not abolished) when the were pre-incubated with N ω -nitro-L-arginine methyl ester (L-NAME). Methods: In this study, effect pharmacological modulation redox environment on investigated. measured using Liquid chromatography tandem mass spectrometry (LC-MS/MS). Results Discussion: Pre-incubation (30 min) GKT137831 (1 μM) caused significant increase in all tissues. HUA, pre-incubation diphenyleneiodonium (DPI) (100 also increases 6-ND. Preincubation HUA hydrogen peroxide (H 2 O ) increased release, whereas catalase (1,000 U/mL) it. superoxide dismutase (SOD) (250 U/mL; 30 either allopurinol or uric acid mM) had no Pre-treatment L-NAME prevented induced by GKT137831, diphenyleneiodonium, H . results obtained indicate major role endogenous H2O2 peroxidases as modulators 6- ND biosynthesis/release lack peroxynitrite contribution.

Language: Английский

Citations

3

The pivotal role of neuronal nitric oxide synthase in the release of 6-nitrodopamine from mouse isolated vas deferens DOI

José Britto‐Júnior,

Samuel Goulart Nacário Silva,

Antonio Tiago Lima

et al.

Nitric Oxide, Journal Year: 2023, Volume and Issue: 143, P. 1 - 8

Published: Dec. 12, 2023

Language: Английский

Citations

5

The effect of (±)-4-NO 2 -propranolol, (±)-7-NO 2 -propranolol, and (±)- propranolol on the rat isolated right atrium DOI Creative Commons

Denis Lima Oliveira,

Vinicius Francisco Cardoso,

José Britto‐Júnior

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 23, 2024

Abstract 6-Nitrodopamine (6-ND) is released from rat isolated atria and has positive chronotropic action, which selectively blocked by β 1 -adrenoceptor antagonists at concentrations that do not affect the effect induced dopamine, noradrenaline, adrenaline. Here effects of (±)-propranolol, (±)-4-NO 2 -propranolol, (±)-7-NO were investigated in right atrium. The atrium was mounted gassed (95%O :5%CO ), heated (37°C) glass chambers, containing Krebs-Henseleit’s solution. Tissues allowed to equilibrate under a resting tension 10mN for hour, isometric registered using PowerLab system. -propranolol caused concentration-dependent falls spontaneous atrial frequency (pEC 50 4.80 ± 0.10, 4.64 4.95 respectively). Noradrenaline (1nM–30µM), adrenaline (1nM–100µM), increases rate. calculated pA values -propranol obtained noradrenaline-induced 8.21 0.35, 6.41 0.21, 8.35 respectively. 6-ND (10pM) (±)-propranolol (1µM), (30nM). (1µM) had no on (10pM)-induced pEC significantly shifted L-NAME treated atria. discrepancy between its respective indicates rate should be attributed b-adrenergic antagonism. finding causes only effect, confirms role this catecholamine as endogenous modulator heart chronotropism.

Language: Английский

Citations

1

The negative chronotropic effects of (±)-propranolol and (±)- 4-NO 2 -propranolol in the rat isolated right atrium are due to blockade of the 6-nitrodopamine receptor DOI Creative Commons

Denis Lima Oliveira,

Vinicius Francisco Cardoso,

José Britto‐Júnior

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: July 29, 2024

Abstract The positive chronotropic action induced by 6-mitrodopamine (6-ND) is selectively blocked β1-adrenoceptor antagonists at concentrations that do not affect the effect dopamine, noradrenaline, and adrenaline. Here effects of (±)-propranolol, (±)-4-NO2-propranolol, (±)-7-NO2-propranolol, were investigated in rat isolated right atrium. atrium was mounted glass chambers containing gassed (95%O2:5%CO2) warmed (37°C) Krebs-Henseleit’s solution, isometric tension registered (PowerLab system). (±)-4-NO2-propranolol caused concentration-dependent falls spontaneous atrial frequency (pIC50 4.80±0.10, 4.64±0.10, 4.95±0.10, respectively). calculated pA2 values for (±)-7-NO2-propranol obtained noradrenaline-induced 8.44±0.08, 6.41±0.07, 9.21±0.29, respectively. chronotropism 6-ND (10pM) (±)-propranolol (1mM), (30nM). (1mM) had no on (10pM)-induced increases rate. pIC50 (±)-7-NO2-propranolol significantly shifted to L-NAME treated atria. discrepancy between its respective indicates rate should be attributed b-adrenergic antagonism. reduced (10µM) unaffected sodium channel inhibitors tetrodotoxin (1µM) lidocaine but abolished atria pre-treated with (10µM). finding causes only effect, confirms role this catecholamine as endogenous modulator heart chronotropism. behaves a selective antagonist

Language: Английский

Citations

0

The negative chronotropic effects of (±)-propranolol and (±)-4-NO2-propranolol in the rat isolated right atrium are due to blockade of the 6-nitrodopamine receptor DOI

Denis Lima Oliveira,

Vinicius Francisco Cardoso,

José Britto‐Júnior

et al.

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 9, 2024

Language: Английский

Citations

0

Neurogenic-derived 6-Nitrodopamine is the Most Potent Endogenous Modulator of the Mouse Urinary Bladder Relaxation DOI
Mariana G. de Oliveira,

José Britto‐Júnior,

Dimária Aparecida Fernandes Dias

et al.

Nitric Oxide, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

Citations

0

6-cyanodopamine as an Endogenous Modulator of Heart Chronotropism and Inotropism DOI Creative Commons

José Britto‐Júnior,

Antonio Tiago Lima,

Denis Lima Oliveira

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 26, 2024

Abstract Purpose- Rat isolated atria and ventricles releases endothelium-derived 6-nitrodopamine this novel catecholamine induces a potent endogenous positive chronotropic inotropic response. 6-Cyanodopamine is released from rabbit ventricles, however it not known whether has any action on the heart. Therefore, was investigated rat release 6-cyanodopamine its Methods- Basal of assessed by LC-MS/MS tyrosine hydroxylase both immunohistochemistry fluorescence in situ hybridization. Chronotropic effects were evaluated in Langendorff’s preparation, respectively. Results- presented basal 6-cyanodopamine, which unaffected pre-treatment with tetrodotoxin. Immunohistochemistry hybridization identified expression endothelium cardiomyocytes. at 10 100 pM induced increases atrial rate, maintained even 30min after preparation washed. In 1min infusion (10 100pM) significantly increased heart frequency, LVDP, dP/dt(max). Bolus injection noradrenaline (1pmol) had no effect LVDP dPdt(max). Infusion (0.01pM) dP/dt(max) when injected end infusion. Conclusion- The results indicate that mediator chronotropism inotropism It potential therapeutic failure may be useful as biomarker pathophysiological processes.

Language: Английский

Citations

0