Effect of arachidonylethanolamide in paraventricular nucleus on cardiac function and sympathetic nerve activity in rats with heart failure

AIM:To determine the roles of the arachidonylethanolamide (AEA) in the paraventricular nucleus (PVN) in cardiac function and sympathetic activity in the rats with chronic heart failure (CHF). METHODS:Chronic heart failure was induced by left coronary ligation in Wistar rats and was confirmed using echocardiography. The rats with CHF and the sham-operated controls (sham group) were treated for 4 weeks with a continuous PVN infusion of AEA, cal-cium-calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) selective inhibitor KN-93, transient receptor potential vanilloid type 1 (TRPV1) channel blocker capsazepine (CPZ), intracellular calcium chelator BAPTA-AM, small-conductance calcium-activated potassium channel (SK channel) blocker apamin and artificial cerebrospinal fluid (vehicle). Sympathetic drive indexes and cardiac function were detected. NG108 cells were incubated with AEA, and then the intracellular cal-cium concentration was measured by fluorometry. The protein expression levels of CaMKⅡ, SK₂ and phosphorylated TRPV1 were determined by Western blot. RESULTS:Compared with sham group, the left ventricular end-diastolic pressure (LVEDP) increased significantly, while peak rate of rise/decline of left ventricular pressure (±dp/dt_max) and ejection fraction (EF) decreased significantly in the CHF group. The concentrations of AEA and intracellular calcium, and the protein levels of CaMKⅡ, SK₂ and phosphorylated TRPV1 in PVN were significantly lower in CHF rats. Compared with the vehicle group, the mortality and sympathetic drive were decreased significantly and cardiac function was improved after treatment with AEA in CHF group. However, PVN perfusion of KN-93, CPZ, BAPTA-AM or apamin contributed to the sympathetic drive and deteriorated the cardiac function. AEA dose-dependently increased intracellular calcium ion concentration, and the protein levels of CaMKⅡ, SK₂ and phosphorylated TRPV1 in NG108 cells. CONCLUSION:AEA in the PVN may be involved in the improvement of cardiac function and sympathetic overdrive via CaMKⅡ/TRPV1/Ca²⁺/SK₂ pathway in rats with CHF.