Effects of artemisinin on HCN channels and pacemaker currents in rabbits with heart failure

Abstract

Objective To observe the effects of artemisinin on hyperpolarization activated cyclic nucleotide-gated (HCN) channels and pacemaker currents (If) in rabbits with heart failure (HF). Methods 30 healthy male New Zealand white rabbits were randomly divided into 3 groups: artemisinin group, HF group and sham group. The rabbit model with HF was established by experimental aortic valve regurgitation and abdominal aortic constriction. Arteminsinin group was given artemisinin 75 mg·kg-1·d-1 intragastrically three times a day, HF group and sham group were fed with 0.5% sodium methylcellulose solution. Heart rate (HR) was measured and echocardiography was performed 4 weeks later. Left ventricular end diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were measured. The whole cell patch clamp technique was used to record the If currents in the voltage clamp mode. The expressions of HCN2 and HCN4 proteins in sinus node were detected by Western blot. Results Compared with sham group, there were significant increases in HR, LVEDD, LVESD, LVEDV, LVESV and decreases in LVEF and LVSF in HF group (all P<0.05). Compared to HF group, significant decreases in HR [(229.3±16.7) bpm vs. (193.2±18.8) bpm], LVEDD [(18.6±1.8) mm vs. (15.4±1.2) mm], LVESD [(14.2±1.7) mm vs. (11.3±1.6) mm], LVEDV [(10.3±1.9) ml vs. (6.7±1.2) ml] and LVESV [(5.2±1.7) ml vs. (3.4±1.3) ml], and increases in LVEF [(42.0±3.0)% vs. (57.0±4.0)%] and LVFS [(22.3±2.0)% vs. (28.9±2.7)%] were observed in artemisinin group (all P<0.05). There was a significant decrease in If current from (1.40±0.24) nA to (0.76±0.11) nA (P<0.05). The expressions of HCN2, HCN4 protein in sinoatrial node decreased significantly in artemisinin group (both P<0.05). Conclusion Artemisinin can decrease If current, HCN protein expression and HR, improve cardiac function and structure in rabbits with HF. Key words: Heart failure; HCN channel; If current; Artemisinin