| Background: Mortality rate of chronic heart failure (CHF) remains high despit optimal therapies and there is still a great need in exploring novel potential therapeutic targets. Recently, results from the African-American Heart Failure Trial (A-HeFT), which demonstrates signficant beneficial effects by a combination of hydralazine (HYD) and isosorbide dinitrate (ISDN) in addition to current optimal therapy, is encourages. In addition, the majority of patients are hypertensive heart disease(HHD), but whether the drug combination in patients who is due to different causes of CHF are different effects. The underlying mechanism remains elusive and the effect of HYD plus ISDN on hypertensive heart disease is unknown.Objective: To investigate whether the additionally use HYD plus ISDN could produce more effects in rats with pressure overload-induced chronic heart failure.Methods: Chronic heart failure was induced by clipping the abdominal aorta. Firstly, sixty-five rats were randomly devided into two groups: sham-operated group (S: sham-operated+NS, n = 10) and aortic stenosis model group ( n = 55). Forty-six rats were still alive at the time that chronic heart failure model was successfully established. The alive rats were further devided into C1 (normal saline, NS), C2 (perindopril 2 mg/kg+bisoprolol fumarate 5 mg/kg), T1(perindopril 2 mg/kg+bisoprolol fumarate 5 mg/kg+isosorbide dinitrate 6 mg/kg+hydralazine 7.2 mg/kg), T2(perindopril 2 mg/kg+bisoprolol fumarate 5 mg/kg+isosorbide dinitrate 26 mg/kg+hydralazine 25 mg/kg). Drugs were administered orally dialy for 12 weeks and rats were sacrificed. Left ventricular ejection fraction (LVEF),left ventricular internal dimension-diastole (LVEDd), left ventricular internal dimension-systole (LVEDs) and left ventricular fractional shortening (LVFS) were assessed by M-mode ultrasound. Left ventricular wight (LVW), heart wight (HW) and body weight (BW) were measured and ratio heart weight to body weight (HW/BW) was calulated. Blood pressure were determined. Serum levels of carboxy-terminal propeptide of procollagen type I (PICP) and carboxy-terminal telopeptide of collagen type I(ICTP)were measured by ELISA according to manufacturer's instruction. Myocardial collagen content was assessed by Masson staining and the collagen volume fraction (CVF) was obtained.Result: Survival rates of rats was the highest in S group, followed by T2 group and C1 group is the least. Echoardiography parameters for LVEF(%): 77.89±5.48, 62.25±11.62, 75.65±1.98, 64.03±6.53, 73.85±5.38, LVEDd(mm): 6.800±1.111, 7.819±0.606, 6.625±0.443, 6.925±0.811, 7.503±0.483, LVEDs (mm): 3.954±0.714, 5.051±1.161, 3.823±0.358, 4.807±0.758, 4.617±0.237, FS(%): 41.78±5.09, 33.80±9.49, 39.50±1.91, 30.78±4.72, 8.28±4.60, respectively for S, C1, C2, T1 and T2 group. Compared with C1 group, most of the parameters exhibited improvements in C2, T1, and T2 groups, but further statistical significance could not be observed among treatment groups, despite a trend showing a further improvement in T2 group probably. Similar results were found in HW/BW, serum level of PICP and ICTP, and CVF.Conclusion: The present study no apparent further benefit from additional adiministration of HYD plus ISDN in rats with pressure overload-induced chronic heart failure. It is possible, or even likely, that the effects about additional adiministration of HYD plus ISDN delay the progress of heart failure were concealed by the beta-blockers, which has a positive effect in fight back heart failure and myocardial remodeling. Further discovery may be found when the HYD plus ISDN group is set up and extend observation time.
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