Changes Of Cardiac Aldosterone And The Long-term Effect Of Recombinant Human Brain Natriuretic Peptide On The Rats With Chronic Heart Failure Induced By Isoproterenol

ObjectiveTo investigate the changes of cardiac aldosterone and mineralocorticoid receptor and the long-term effect of recombinant human Brain Natriuretic Peptide(rhBNP) on rats with chronic heart failure(CHF) induced by isoproterenol(ISO).MethodsExperimental CHF was created in SD(Sprangue-dawly)rats by subcutaneous injection of isoproterenol, the survivors were randomly divided into CHF group (n=9),rhBNP treatment groups(BNP-L,BNP-H subgroup; rats respectively received subcutaneous injection of rhBNP 22.5ug-1·kg-1·d-1, 45ug-1·kg-1·d-1,n all=8), and age, gender and weight matched SD rats were set as control group(n=10).After 1 month intervention, all rats were sacrificed after Echocardiography and hemodynamics measurement and haemospasia from inferior vena cava to detect the plasma concentration of aldosterone. Morphological characteristics were measured with HE, Sirus-red staining. Content of ventricular collagen was assessed with compute-assisted image analysis system (Image-Pro Plus, Version:6.0). Radiation immunological test were performed to detect the concentration of aldosterone in both plasma and the heart.The transcriptional levels of aldosterone synthase (CYP11B2) and Mineralocorticoid Receptor(MR) were evaluated by Real Time-polymerasechain reaction(RT-PCR).MR were extracted and measured by western blot analysis and labled with immunohistochemistry staining.Results1 Left ventricular internal diameter at end-diastole (LVIDd) and Left ventricular internal diameter at end-systole(LVIDs) of CHF group were higher than those of control group(7.35±0.70 vs 5.66±0.18mm;5.84±0.21 vs 3.06±0.51mm,P all<0.01), ejection fraction(EF%) was much lower than that of control group(38.75±4.04 vs 79.38±4.57, P <0.01); LVIDd and LVIDs of treatment groups were lower than those of CHF group(P<0.01), EF(%) were higher than that of CHF group(P<0.01).2 Left ventricular end diastolic pressure(LVEDP) of CHF group were higher than that of control group(8.46±1.29 vs 3.58±1.21mmHg, P<0.01), left ventricular systolic pressure (LVSP ) and±maximum rate of left ventricular pressure rise/ decay (±dp/dtmax) were much lower than those of control group(94.30±5.6 vs112.1±7.42 mmHg;7164.39±502.58 vs 10199.53±462.87 mmHg/s;5646.23±590.52 vs 9056.54±985.24 mmHg/s,P all<0.01); LVEDP of the treatment groups were lower than that of CHF group(P<0.05),±dp/dtmax were higher than those of CHF group(P<0.05 or P<0.01); LVSP of BNP-L were not different from that of CHF group, LVSP of BNP-H were higher than that of CHF group(P<0.05).3 The collage volume fraction(CVF%) of CHF group were higher than that of control group(20.21±2.50 vs 3.75±0.55,P<0.01), the CVF(%) of treatment groups were lower than that of CHF group(18.24±2.22,17.36±2.21 vs 20.21±2.50,P<0.05).4 The concentration of aldosterone both in plasma and local heart of CHF group were higher those of control group(0.63±0.06 vs 0.3±0.07ng/ml,0.41±0.05 vs 0.08±0.01ng/mg pro,P<0.01); both of the indexes of treatment groups were lower than those of the CHF group(0.54±0.09,0.53±0.07 vs 0.63±0.06 ng/ml;0.36±0.06,0.31±0.04 vs 0.41±0.05 ng/mg pro,P<0.05 or P<0.01)5 The mRNA levels of CYP11B2 and MR in CHF group were higher than those in control group(P<0.01); the mRNA levels of CYP11B2 and MR in treatment groups were lower than those in CHF group(P<0.05 or P<0.01).6 With Western Blot and immunohistochemistry staining respectively, the protein expression level of MR in CHF group were higher than that in control group(P<0.01);the protein expression levels of MR in treatment groups were lower than that in CHF group (P<0.01) . Conclusions1 The mRNA transcription of CYP11B2 and the cardiac aldosterone as well as MR were increased in SD rats with CHF induced by isoproterenol; the cardiac fibrosis was increased, and the heart function was decreased in rats with CHF. The results indicated that aldosterone may play an important role in heart failure.2 Chronic treatment of BNP can improved the hemodynamics of SD rats with CHF induced by isoproterenol. The mechanism of BNP may be the following, it downregulated the transcription of CYP11B2 and reduced the production of cardiac aldosterone as well as MR expression in failing heart.