Role of nitric oxide in cardiac arrhythmias during Hypothyroidism

• Grant number: 19/18918-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2021
• End date: August 16, 2023
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Danilo Roman Campos
• Grantee: Diego Santos de Souza
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

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)

Scientific publications

(14)

(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)

GILMARA BEATRIZ ANDRADE DA SILVA; DIEGO SANTOS SOUZA; JOSÉ EVALDO RODRIGUES MENEZES-FILHO; JÚLIO ALVES DA SILVA-NETO; JADER DOS SANTOS CRUZ; DANILO R. ROMAN-CAMPOS; LUCINDO JOSÉ QUINTANS-JÚNIOR; CARLA MARIA LINS DE VASCONCELOS. A (-)-Carvona Modula a Sinalização de Cálcio Intracelular com Ação Antiarrítmica em Corações de Ratos. Arquivos Brasileiros de Cardiologia, v. 119, n. 2, p. 294-304, 2022-08-05. (19/21304-4, 19/18918-0)

GONCALVES, MEIRE S. S.; SILVA, ERIC AIAN P.; SANTOS, DANILLO M.; SANTANA, IZABEL R.; SOUZA, DIEGO S.; ARAUJO, ANDREZA M.; HEIMFARTH, LUANA; VASCONCELOS, CARLA M. L.; SANTOS, VINICIUS C. O.; SANTOS, V, MARCIO R.; et al. erolidol attenuates isoproterenol-induced acute myocardial infarction in rat. NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, v. 395, n. 3, p. 353-363, MAR 2022. (19/18918-0)

TEIXEIRA-FONSECA, JORGE LUCAS; SANTOS-MIRANDA, ARTUR; MARQUES, IVAN LOBO SOUSA; MARQUES, LEISIANE PEREIRA; ALCANTARA, FABIANA; CONCEICAO, MICHAEL RAMON DE LIMA; SOUZA, DIEGO SANTOS; GONDIM, ANTONIO NEI SANTANA; ROMAN-CAMPOS, DANILO. Eugenol delays the onset of ouabain-induced ventricular cardiac arrhythmias in guinea pigs. BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY, v. N/A, p. 11-pg., 2023-09-19. (21/15122-0, 20/14635-1, 21/05584-7, 19/18918-0)

SOUZA, DIEGO SANTOS; MARQUES, LEISIANE PEREIRA; COSTA, ALEXANDRE DANTAS; CRUZ, JADER SANTOS; RHANA, PAULA; SANTOS-MIRANDA, ARTUR; JOVIANO-SANTOS, JULLIANE VASCONCELOS; DURCO, AIMEE OBOLARI; LINS VASCONCELOS, CARLA MARIA; ROMAN-CAMPOS, DANILO. Experimental hypothyroidism induces cardiac arrhythmias and ranolazine reverts and prevents the phenotype. Life Sciences, v. 308, p. 13-pg., 2022-09-13. (20/14635-1, 21/05584-7, 19/21304-4, 19/18918-0)

ROMAN-CAMPOS, DANILO; SALES-JUNIOR, POLICARPO; COSTA, ALEXANDRE D.; SOUZA, DIEGO SANTOS; SANTOS-MIRANDA, ARTUR; JOVIANO-SANTOS, JULLIANE, V; ROPERT, CATHERINE; CRUZ, JADER S.. Impact of IFN-gamma Deficiency on the Cardiomyocyte Function in the First Stage of Experimental Chagas Disease. MICROORGANISMS, v. 10, n. 2, p. 7-pg., 2022-02-01. (19/18918-0, 18/22830-9, 19/21304-4, 18/20777-3)

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; et al. 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. (19/21304-4, 19/18918-0)

MARQUES, LEISIANE P.; JOVIANO-SANTOS, JULLIANE, V; SOUZA, DIEGO S.; SANTOS-MIRANDA, A.; ROMAN-CAMPOS, D.. Cardiotoxicity of pyrethroids: molecular mechanisms and therapeutic options for acute and long-term toxicity. BIOCHEMICAL SOCIETY TRANSACTIONS, v. N/A, p. 15-pg., 2022-10-31. (21/15122-0, 21/05584-7, 19/18918-0)

SANTOS-MIRANDA, ARTUR; JOVIANO-SANTOS, V. JULLIANE; CRUZ-NASCIMENTO, TAYNARA; NERI, ELIDA ADALGISA; SOUZA, DIEGO SANTOS; MARQUES, LEISIANE PEREIRA; KRIEGER, JOSE E.; ROMAN-CAMPOS, DANILO. The fungicide Tebuconazole induces electromechanical cardiotoxicity in murine heart and human cardiomyocytes derived from induced pluripotent stem cells. Toxicology Letters, v. 359, p. 10-pg., 2022-04-15. (18/22830-9, 19/18918-0, 21/05584-7, 19/21304-4, 20/14635-1, 18/20777-3)

MIGUEL-DOS-SANTOS, RODRIGO; SOUZA, DIEGO SANTOS; MESQUITA, THASSIO. Fine-tuning SERCA activity to treat distinct heart failure syndromes. JOURNAL OF PHYSIOLOGY-LONDON, v. 599, n. 18, p. 2-pg., 2021-08-23. (19/18918-0)

PINA, LICIA T. S.; RABELO, THALLITA K.; TRINDADE, GABRIELA G. G.; ALMEIDA, IGGO K. S.; OLIVEIRA, MARLANGE A.; DOS SANTOS, PRISCILA L.; SOUZA, DIEGO SANTOS; DE MENEZES-FILHO, JOSE E. R.; LINS DE VASCONCELOS, CARLA MARIA; SANTOS, SANDRA L.; et al. gamma-Terpinene complexed with beta-cyclodextrin attenuates spinal neuroactivity in animals with cancer pain by Ca2+ channel block. Journal of Pharmacy and Pharmacology, v. 74, n. 11, p. 11-pg., 2022-08-17. (19/18918-0)

RHANA, PAULA; BARROS, GUILHERME MENDES; SANTOS, VINICIUS CISNEIROS DE OLIVEIRA; COSTA, ALEXANDRE DANTAS; DOS SANTOS, DANILLO MENEZES; FERNANDES-BRAGA, WESLLEY; DURCO, AIMEE OBOLARI; SANTOS, MARCIO ROBERTO VIANA; ROMAN-CAMPOS, DANILO; DE VASCONCELOS, CARLA MARIA LINS; et al. S-limonene protects the heart in an experimental model of myocardial infarction induced by isoproterenol: Possible involvement of mitochondrial reactive oxygen species. European Journal of Pharmacology, v. 930, p. 11-pg., 2022-07-18. (19/18918-0, 19/21304-4)

MARINHO, YANDRA Y. M.; SILVA, ERIC AIAN P.; OLIVEIRA, JEFERSON Y. S.; SANTOS, DANILLO M.; LIMA, BRUNO S.; SOUZA, DIEGO S.; MACEDO, FABRICIO N.; SANTOS, ANNA C. R. S.; ARAUJO, ADRIANO A. S.; VASCONCELOS, CARLA M. L.; et al. Preparation, physicochemical characterization, docking and antiarrhythmic effect of D-limonene and D-limonene hydroxypropyl-beta-cyclodextrin complex. JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, v. 71, p. 8-pg., 2022-05-01. (19/18918-0)

DA SILVA, MARIA VITORIA; SANTOS-MIRANDA, ARTUR; JOVIANO-SANTOS, JULLIANE, V; SOUZA, DIEGO SANTOS; MARQUES, LEISIANE PEREIRA; SARMENTO, JAQUELINE OLIVEIRA; BESERRA, SAMUEL SANTOS; ROMAN-CAMPOS, DANILO. The insecticide beta-Cyfluthrin induces acute arrhythmic cardiotoxicity through interaction with NaV1.5 and ranolazine reverses the phenotype. Clinical Science, v. 136, n. 5, p. 15-pg., 2022-03-01. (21/05584-7, 19/18918-0, 18/20777-3, 18/22830-9, 20/09403-4, 19/21304-4)

TEIXEIRA-FONSECA, JORGE LUCAS; JOVIANO-SANTOS, JULLIANE V.; BESERRA, SAMUEL SANTOS; CONCEICAO, MICHAEL RAMON DE LIMA; LEAL-SILVA, POLYANA; MARQUES, LEISIANE PEREIRA; SOUZA, DIEGO SANTOS; ROMAN-CAMPOS, DANILO. Exploring the involvement of TASK-1 in the control of isolated rat right atrium function from healthy animals and an experimental model of monocrotaline-induced pulmonary hypertension. NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, v. N/A, p. 14-pg., 2023-06-20. (19/21304-4, 19/18918-0, 21/15122-0, 20/14635-1, 21/05584-7)