| ObjectiveTo study the changes of natriuretic peptide receptor (NPR) and myocardial fibrosis in rats with chronic heart failure(CHF) induced by isoproterenol.To explore the effect and mechanism of long-term therapy with recombinant form of human brain natriuretic peptide (rhBNP) for CHF.MethodsExperimental CHF model was induced by Isoprenaline in Sprangue dawly (SD) rats. After the model being created ,CHF rats were randomly divided into the following 3 groups;(1)heart failure group (HF,n=10);(2)rhBNP low dose group (L,n=8);(3)rhBNP high dose group (H,n=8);Ten age and sex matched SD rats were randomized to contorl group(C,n=10).After 30 days intervention the rats were perfromed with echocardiography and measured hemodynamics.The wet-to-dry ratio of lungs was calculatde.Morphological characteristics were evaluated with HE,Sirs-red staining.The collagen volume fraction(CVF) of lefe ventricular were assessed and calculated with compute-assisted image analysis system (Image-ProPlus, Version:6.0);The contents of cyclic guanosine monophosphatewere (cGMP) both inplasma and myocardium were measured with radioimmunoassay. The expression of natriuretic peptide receptors including A-type natriuretic peptide receptor (NPR-A),B-type natriuretic peptide receptor (NPR-B) and C- typenatriuretic peptide receptor (NPR-C) were assessed with both Immunohistochemistry staining and western blot analysis.Results1 The left ventricular end-diastolic diameter (LVIDd)and left ventricular end-diastolic pressure (LVEDP)were dramtically increased in HF group compared with C group(P<0.01),but they were dramtically decreased in both L and H groups compared with HF group(P<0.01),and there were no different between L and H groups (P>0.05).Left ventricular ejection fraction (EF), left ventricular systolic pressure (LVSP) and left ventricular pressure and the largest increase in the largest decline rate (±dp / dt) were lower in HF group than C group(P<0.01);but they were higher in L and H groups than HF group (P<0.01).2 The wet-to-dry ratio of lung was higher in HF group than that in C group (P<0.01),but it was dramtically decreased in L and H groups compared with HF group(P<0.01),and there was no different between L and H groups (P>0.05).3 The left ventricle of CVF was significantly increased in HF group compared with C group(P<0.01),but it was dramtically decreased in both L and H groups compared with HF group,and there was no different between L and H groups (P>0.05).4 The contents of cGMP both in the plasm and left ventricular myocardium were lower in HF group than that in C group(P<0.01),but they were dramtically increased in L and H groups compared with HF group(P<0.01),and there was no significant difference between L and H groups(P>0.05).5 Both NPR-A and NAP-B expression in left ventricular myocardium were lower in HF group than those in C group(P<0.01),but they were dramtically increased in L and H groups compared with HF group(P<0.01), The NPR-A expression was significantly increase in H groups compared with L group (P<0.01) ;The NPR-B expression was no difference between L and H groups(P>0.05). The NPR-C expression in left ventricular myocardium was significantly increased in HF group compared with C group (P<0.01), but they were dramtically decreased in both L and H groups compared with HF group(P<0.01), however, there was no significant difference between L and H groups(P>0.05).Conclusions1 NPR-A, NPR-B expression down-regulate and NPR-C expression up-regulate in the left ventricular myocardium of rats with chronic heart failure induced by isoprenaline.They lead to inhibition of the cGMP production in the plasm and in left ventricular myocardium, and enhance myocardial fibrosis.2 The long-term therapy of exogenous BNP for rats with CHF induced by isoprenaline can attunate myocardial fibrosis and improved heart function by up-regulation of NPR-A, NPR-B,down-regulation of NPR-C and then raise the contents of cGMP both in the plasm and in left ventricular myocardium.
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