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Role of nitric oxide in cardiac arrhythmias during Hypothyroidism

Grant number: 19/18918-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): April 01, 2021
Effective date (End): March 31, 2023
Field of knowledge:Biological Sciences - Pharmacology - Cardiorenal Pharmacology
Principal researcher:Danilo Roman Campos
Grantee:Diego Santos de Souza
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil


Cardiac Arrhythmias are among the diseases that most lead to disability and sudden death worldwide, and thyroid diseases, especially Hypothyroidism, play a prominent role. Thyroid hormones regulate the expression of myocardial genes that control intracellular calcium handling, leading to altered excitation-contraction coupling and heart function. Hypothyroidism is known to lead to a reduction in cardiomyocyte length, reduction of sarcoplasmic reticulum Ca2 + ATPase (SERCA) expression with increased expression of its inhibitor - phospholambam, reduction of intracellular calcium transient. Taken together, these changes culminate in an altered spatial and temporal dynamics of the Ca2 + cycle. Several molecules have the ability to modulate the excitation-contraction coupling in diseases, among them the Nitric Oxide (NO). It is synthesized by Nitric Oxide Synthases (NOS), which are have three distinct isoforms, namely: endothelial (eNOS), neuronal (nNOS) and induced (iNOS). We know that Hypothyroidism increases iNOS activity in rat ventricles leading to a reduction in ejection fraction during adrenergic stimulation. However, little is known about the participation of eNOS and nNOS during Hypothyroidism and how they contribute to the change in NO dynamics and their role in controlling cardiac function, especially intracellular calcium handling in cardiomyocytes. Therefore, we aim to investigate whether Hypothyroidism causes cardiac dysfunction through the NO signaling pathway. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ELASORU, SEYI ELIJAH; RHANA, PAULA; DE OLIVEIRA BARRETO, TATIANE; DE SOUZA, DAYANE LORENA NAVES; MENEZES-FILHO, JOSE EVALDO RODRIGUES; SOUZA, DIEGO SANTOS; MOREIRA, MATHEUS VILARDO LOES; CAMPOS, MARCO TULIO GOMES; ADEDOSU, OLANIYI TEMITOPE; ROMAN-CAMPOS, DANILO; MELO, MARILIA MARTINS; CRUZ, JADER SANTOS. Andrographolide protects against isoproterenol-induced myocardial infarction in rats through inhibition of L-type Ca2+ and increase of cardiac transient outward K+ currents. European Journal of Pharmacology, v. 906, SEP 5 2021. Web of Science Citations: 0.

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