The Mechanism of Isoproterenol Hydrochloride-Induced Cardiac Arrhythmia and the Effect of Propranolol Through the CaMKII Pathway

Abstract

Abstract Background Ventricular arrhythmia (VA) is a common clinical disease that is associated with high morbidity and mortality. Calcium/calmodulin-dependent protein kinase II (CaMKII) is critical in regulating cardiac electrophysiological functions. Research shows that propranolol can significantly antagonizes VA. However, it is unclear whether propranolol can regulate CaMKII, thereby inhibiting VA. Aims The present study aimed to clarify the molecular mechanism by which propranolol inhibits VA through the CaMKII pathway. Methods A total of 60 healthy Sprague Dawley rats were randomly divided into the control and experimental groups (model and propranolol group) that were given corresponding treatment. Isoproterenol hydrochloride (ISO) was administered to induce VA. The ECG was monitored for 1 hour, and the VA incidence was calculated. The heart weight/body weight (HW/BW) ratio was calculated manually. The levels of Ca2+, cTnI, oxidative stress, Inflammatory factors were studied.Calcium pump (SERCA2) and CaMKIIδ mRNA were detected by Real-time PCR. Western blotting was used to assess CaMKII, oxidized CaMKII (OX-CaMKII), phosphorylated phosphoprotein (P-PLB) and SERCA2. Results There was no obvious abnormality in the control group. Compared with the control group rats, the indexes of rats in model group changed significantly (P < 0.01). Compared with the model group rats, the indexes of rats in the propranolol was significantly improved (P < 0.01 or P < 0.05 ). Conclusions Collectively, propranolol antagonized VA effect by reducing CaMKII expression and activating SERCA2, thereby reducing the Ca2 + load .