Exercise Regulated Cardiac Sympathetic Nerve Function in Chronic Heart Failure Rat——The Role of Norepinephrine Transporter

Objective:The present study was to investigate whether norepinephrine transporter (NET) play an important role in exercise-induced improvement of sympathetic nerve function, heart function and exercise tolerance in chronic heart failure rats.Methods:Post myocardial infarction (MI) heart failure model was established by ligating anterior descending branch of coronary artery of rats.After 4 weeks rest, animals were randomly divided into 4 groups:sham operation sedentary (Sham) , sham operation plus exercise (Sham+E) , sedentary MI (MI) and MI plus exercise (MI+E) , among which Sham+E and MI+E performed a 10-week treadmill exercise while Sham and MI retained their own daily activity.After the end of experiment, exhaust time was determined during incremental treadmill test;left ventricular end-systolic diameter (LVESD) , left ventricular end-diastolic diameter (LVEDD) , heart rate (HR) , fractional shortening (FS) and left ventricular ejection fraction (LVEF) were measured using echocardiography;heart tissue was collected for histopathology study by Masson staining;myocardial and plasma norepinephrine (NE) were measured;cardiac sympathetic ganglion and myocardial NET mRNA level were determined by real-time fluorescent quantitation PCR and NET protein of myocardium was measured by Western blot.Results:Fourteen week after surgery, HW/BW and LVEF increased, HR decreased and exhausted time extended in Sham+E compared with Sham.Heart weight (HW) , heart weight/body weight (HW/BW) , LVESD and LVEDD raised, FS and LVEF lowered, myocardial and plasma NE elevated, NET mRNA of sympathetic ganglion and NET protein level of myocardium decreased, exhaust time reduced in MI compared with Sham.BW lowered, HW and HW/BW raised, LVESD and LVEDD slightly decreased, FS and LVEF had no significant change, myocardial and plasma NE reduced, NET mRNA of sympathetic ganglion and NET protein level of myocardium increased, exhaust time extended in MI+E compared with MI (NE, NET mRNA and protein level had not significantly difference between MI+E and Sham) .Conclusion:Long-tern aerobic exercise training reduced and restored NE discharge of sympathetic nerve ending through up-regulated NET expression of cardiac sympathetic ganglion, as a result, excessive sympathetic excitement improved and exercise tolerance enhanced.