Abstract
Ventricular arrhythmia (VA) is a major component of sudden cardiac death (SCD). To investigate the expression of brain natriuretic peptide (BNP), endothelin-1 (ET-1), and transforming growth factor-beta 1 (TGF-β1) during VA, we established a rat model of VA induced by BaCl2 solution through a microinjector pump. PD142893 (ET-1 receptor blocker) and SB431542 (TGF-β1 receptor type I blocker) were used to explore the effect of ET-1 and TGF-β1 on BNP expression in the myocardium after VA. BNP, ET-1, and TGF-β1 in rat myocardium were assayed by western blot and immunohistochemical staining for proteins, and real-time quantitative polymerase chain reaction for mRNAs. We found increased expression of BNP and ET-1 in rat myocardium that was associated with the duration of VA. However, TGF-β1 protein expression remained unchanged. Such early increases in BNP and ET-1 may be attributed to fatal arrhythmias associated with SCD, suggesting these may be novel biomarkers of this disease. After intraperitoneal injection of PD142893 and SB431542, respectively, BNP was downregulated in the myocardium of the left ventricle; however, this was abrogated by co-application of the two inhibitors. These results suggested that both ET-1 and TGF-β1, by specifically binding to their receptors, might be involved in the myocardial synthesis of BNP during VA in vivo.