Pharmacological Modulation of the Ca[sup.2+]/cAMP/Adenosine Signaling in Cardiac Cells as a New Cardioprotective Strategy to Reduce Severe Arrhythmias in Myocardial Infarction

• Published in: Pharmaceuticals (Basel, Switzerland) Vol. 16; no. 10
• Main Authors: Tallo, Fernando Sabia, de Santana, Patricia Oliveira, Pinto, Sandra Augusta Gordinho, Lima, Rildo Yamaguti, de Araújo, Erisvaldo Amarante, Tavares, José Gustavo Padrão, Pires-Oliveira, Marcelo, Nicolau, Lucas Antonio Duarte, Medeiros, Jand Venes Rolim, Taha, Murched Omar, David, André Ibrahim, Luna-Filho, Bráulio, Filho, Carlos Eduardo Braga, Barbosa, Adriano Henrique Pereira, Silva, Célia Maria Camelo, Wanderley, Almir Gonçalves, Caixeta, Adriano, Caricati-Neto, Afonso, Menezes-Rodrigues, Francisco Sandro
• Format: Journal Article
• Language: English
• Published: MDPI AG 01.10.2023
• Subjects: Arrhythmia; Cardiac glycosides; Cardiotonic agents; Complications and side effects; Cyclic adenylic acid; Dosage and administration; Drug therapy; Health aspects; Heart attack; Physiological aspects; Prevention; Risk factors; Testing; Brazil
• ISSN: 1424-8247; 1424-8247
• DOI: 10.3390/ph16101473

Acute myocardial infarction (AMI) is the main cause of morbidity and mortality worldwide and is characterized by severe and fatal arrhythmias induced by cardiac ischemia/reperfusion (CIR). However, the molecular mechanisms involved in these arrhythmias are still little understood. To investigate the cardioprotective role of the cardiac Ca[sup.2+] /cAMP/adenosine signaling pathway in AMI, L-type Ca[sup.2+] channels (LTCC) were blocked with either nifedipine (NIF) or verapamil (VER), with or without A[sub.1] -adenosine (ADO), receptors (A[sub.1] R), antagonist (DPCPX), or cAMP efflux blocker probenecid (PROB), and the incidence of ventricular arrhythmias (VA), atrioventricular block (AVB), and lethality (LET) induced by CIR in rats was evaluated. VA, AVB and LET incidences were evaluated by ECG analysis and compared between control (CIR group) and intravenously treated 5 min before CIR with NIF 1, 10, and 30 mg/kg and VER 1 mg/kg in the presence or absence of PROB 100 mg/kg or DPCPX 100 µg/kg. The serum levels of cardiac injury biomarkers total creatine kinase (CK) and CK-MB were quantified. Both NIF and VER treatment were able to attenuate cardiac arrhythmias caused by CIR; however, these antiarrhythmic effects were abolished by pretreatment with PROB and DPCPX. The total serum CK and CK-MB were similar in all groups. These results indicate that the pharmacological modulation of Ca[sup.2+] /cAMP/ADO in cardiac cells by means of attenuation of Ca[sup.2+] influx via LTCC and the activation of A[sub.1] R by endogenous ADO could be a promising therapeutic strategy to reduce the incidence of severe and fatal arrhythmias caused by AMI in humans.