Resiniferatoxin reduces cardiac sympathetic nerve activation to exert a cardioprotective effect during myocardial infarction.

BACKGROUND AND OBJECTIVE

Myocardial infarction (MI) is a common critical disease of the cardiovascular system. The process of MI is often accompanied by the excessive activation of cardiac sympathetic nerves, which leads to arrhythmia. Resiniferatoxin (RTX) is a transient receptor potential vanilloid 1 (TRPV1), involved in the cardiac sympathetic afferent reflex. However, whether RTX can reduce the occurrence of arrhythmia and exert a cardioprotective effect by inhibiting the sympathetic reflex during MI is still unknown.

METHODS

The left anterior descending artery of cardiac was clamped to construct a model of MI. RTX (50 μg/ml) was used by epicardial application in MI rats. Ventricular electrophysiologic properties were continuously monitored by a body surface ECG. Yrosine hydroxylase (TH) and growth associated protein 43 (GAP43) were detected by Immunofluorescence staining. Connexin43 and transforming growth factor beta receptor 1 (TGF-β1) were detected by western blot. Norepinephrine (NE) and BNP levels in blood and tissue were determined by ELISA. Cardiac function was assessed by echocardiography.

RESULTS

The ERP, APD90, QRS, QT and the Tend-Tpeak intervals in MI rats were all prolonged, but decreased after RTX treatment ( = 3, <0.05). In contrast, the RR interval was shortened in the MI group, but prolonged in the MI+RTX group ( = 3, <0.05). RTX treatment significantly reduced ventricular arrhythmias after MI. TH- and GAP43-positive nerve densities and TGF-β1, and cx-43 protein expression were up-regulated in the MI group compared to the sham group, and they were decreased in the MI+RTX group compared to the MI group ( = 3, <0.05). RTX can decrease serum and tissue NE and BNP levels ( = 3, <0.05). RTX pretreatment significantly decreased heart rate, HW/BW ratio and LVIDS, and increased LVEF andLVFS values ( = 3, <0.05).

CONCLUSION

RTX improved cardiac dysfunction, ventricular electrophysiologic properties, and sympathetic nerve remodeling in rats with MI by inhibiting the excessive cardiac sympathetic drive.