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

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Britto-Junior, Jose ; Lima, Antonio Tiago ; Oliveira, Denis Lima ; Mariano, Fernanda, V ; de Souza, Valeria Barbosa ; Schenka, Andre Almeida ; Peterson, Larryn W. ; Slot, Maria Skovbjerg ; Fjord, Rebecca ; Wang, Tobias ; Antunes, Edson ; De Nucci, Gilberto
Total Authors: 12
Document type: Journal article
Source: Life Sciences; v. 366, p. 13-pg., 2025-02-24.
Abstract

Rat isolated atria and ventricles release endothelium-derived 6-nitrodopamine, which induces potent positive chronotropic and inotropic responses. 6-Cyanodopamine is released from rabbit isolated atria and ventricles; however, it is not known whether this novel catecholamine has any action on the isolated heart. Therefore, it was investigated whether rat isolated ventricles release 6-cyanodopamine and its action on the rat isolated heart. Basal release of 6-cyanodopamine was assessed by LC-MS/MS method. Tyrosine hydroxylase expression was measured by both immunohistochemistry and fluorescence in situ hybridization (FISH). Chronotropic and inotropic effects were evaluated in isolated atria and Langendorff's preparation, respectively. Rat isolated ventricles presented basal release of 6-cyanodopamine, which was unaffected by pre-treatment with the voltage-gated sodium channel blocker tetrodotoxin. Immunohistochemistry and FISH assays identified tyrosine hydroxylase expression in both endothelium and cardiomyocytes. 6-Cyanodopamine at 10 and 100 pM significantly increased the atrial rate, which was maintained even at 30 min after washing the preparation. In the Langendorff's preparation, 1-min infusion of 6-cyanodopamine (10 and 100 pM) significantly increased heart frequency, left ventricular developed pressure (LVDP), and maximal rate of rise of the left ventricular pressure (dP/dtmax). Bolus injection of noradrenaline at 1 pmol had no effect on any of these parameters; however, in the presence of 6-cyanodopamine (0.01 pM), noradrenaline (1 pmol) significantly increased heart frequency, LVDP, and dP/dt(max). The results indicate that 6-cyanodopamine is a potent endogenous catecholamine mediating both chronotropism and inotropism in the rat isolated heart. 6-Cyanodopamine may have potential therapeutic effect in heart failure and may be useful as a biomarker of cardio-renal diseases. (AU)

FAPESP's process: 21/13726-6 - Identification of molecules related to the synthesis of adrenaline, noradrenaline and dopamine in the endothelium of reptiles and mammals by immunohistochemistry and in situ hibridization
Grantee:Valéria Barbosa de Souza
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 19/16805-4 - Evaluation of the pathophysiological role of endothelial catecholamines
Grantee:Gilberto de Nucci
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 21/13593-6 - Evaluation of chronic 6-nitrodopamine treatment in rats
Grantee:Antonio Tiago Silva Lima
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 17/15175-1 - Modulation of soluble guanylate cyclase and the intracellular levels of cyclic nucleotides in the lower urinary tract and prostate
Grantee:Edson Antunes
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 23/16075-1 - Characterization of the 6-ND receptor through in vitro evaluation of nitrated analogues of propranolol and atenolol without positive chronotropic effects induced by 6-nitrodopamine, dopamine, noradrenaline and adrenaline.
Grantee:Denis Lima Oliveira
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 23/04217-6 - A reappraisal of the regulatory role of the endothelium over the cardiovascular system from a comparative perspective
Grantee:Gilberto de Nucci
Support Opportunities: Research Grants - Visiting Researcher Grant - International
FAPESP's process: 21/14414-8 - Evaluation of the action of nitro-catecholamines in the cardiovascular system
Grantee:José Britto Júnior
Support Opportunities: Scholarships in Brazil - Post-Doctoral