Pharmacological Modulation of the Ca²⁺/cAMP/Adenosine Signaling in Cardiac Cells as a New Cardioprotective Strategy to Reduce Severe Arrhythmias in Myocardial Infarction

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Tallo, Fernando Sabia ; de Santana, Patricia Oliveira ; Pinto, Sandra Augusta Gordinho ; Lima, Rildo Yamaguti ; de Araujo, Erisvaldo Amarante ; Tavares, Jose Gustavo Padrao ; Pires-Oliveira, Marcelo ; Nicolau, Lucas Antonio Duarte ; Medeiros, Jand Venes Rolim ; Taha, Murched Omar ; David, Andre Ibrahim ; Luna-Filho, Braulio ; Braga Filho, Carlos Eduardo ; Barbosa, Adriano Henrique Pereira ; Silva, Celia Maria Camelo ; Wanderley, Almir Goncalves ; Caixeta, Adriano ; Caricati-Neto, Afonso ; Menezes-Rodrigues, Francisco Sandro

• Tipo de documento: Artigo Científico
• Fonte: PHARMACEUTICALS; v. 16, n. 10, p. 13-pg., 2023-10-01.

Resumo

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 Ca2+/cAMP/adenosine signaling pathway in AMI, L-type Ca2+ channels (LTCC) were blocked with either nifedipine (NIF) or verapamil (VER), with or without A(1)-adenosine (ADO), receptors (A(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 mu g/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 Ca2+/cAMP/ADO in cardiac cells by means of attenuation of Ca2+ influx via LTCC and the activation of A(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. (AU)

• Processo FAPESP: 17/25565-1 - Nova abordagem terapêutica da doença de Parkinson: Neuroproteção estimulada pela modulação farmacológica da sinalização intracelular pelo Ca2+/AMPc/NO
• Beneficiário: Afonso Caricati Neto
• Modalidade de apoio: Auxílio à Pesquisa - Regular