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

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Life sciences Pub Date : 2025-02-19 DOI:10.1016/j.lfs.2025.123504

José Britto-Júnior , Antonio Tiago Lima , Denis Lima Oliveira , Fernanda V. Mariano , Valéria Barbosa de Souza , André Almeida Schenka , Larryn W. Peterson , Maria Skovbjerg Slot , Rebecca Fjord , Tobias Wang , Edson Antunes , Gilberto De Nucci

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引用次数: 0

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/dt_max). 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.

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.