The Study Of Calcineurin-dependent Inducement Mechanism Of Cardiac Hypertrophy In Rats

Background and Objective: Cardiac hypertrophy serves as a common passway in various cardiovascular diseases. It is one of the most important pathological foundations resulting in cardiogenic death. Recently, cardiac hypertrophy caused by the maladjustment of neural and humoral factors, especially renin-angiotensin-aldosterone system (RAAS) has been paid much attention. It has been detected that aldosterone is an important factor which can induce cardiac hypertrophy. But its detail mechanism remains unclear. It has been showed that CaN-dependent signal passway may play an important role in the development of cardiac hypertrophy. However, whether CaN-dependent signal passway is involved into all kinds of cardiac hypertrophy induced by various stimuli? In the present study we have made two animal models of cardiac hypertrophy by way of either aldosterone injected intraperitoneally or operation of "one kidney one clip (1K1C)". In order to detect the role of CaN in the mechanism of cardiac hypertrophy induced by aldosterone, we observed the effects on hypertrophy by interfered with CsA or spironolactone (spiro) including the ratio of heart weight to body weight, changes of gene expression related to cardiac hypertrophy-atrial natriuretic factor (ANF) and -myosin heavy chain( -MHC), the activity of CaN and its geneexpression in heart tissue. Our study includes three parts:Part I The effects of ectogenesis aldosterone on CaN activity in the tissue of important organs and its regulation in ratsTwenty-one Wistar rats were divided into three groups randomly. Two groups treated with aldosterone injected intraperitoneally were interfered with spironolactone and normal saline respectively while placebo with normal Salin only. The concentrations of plasma Aldosterone (Ald), angiotensin II (Angll), endothelins (ET-1) and the activity of CaN in the tissues of important organs were measured. The result was that the sequence of tissue CaN activity in organs from strong to weak was spleen, kidney, liver, brain, lung, aorta and heart. Exogenous aldosterone raised CaN activity especially in heart. Spironolactone depressed increase of CaN activity caused by exogenous aldosterone. On the other hand, exogenous aldosterone increased aldosterone plasma concentration notably and decreased NO3". plasma concentration. Spironolactone intervention could decrease significantly the ratio of Aid -, AngIKET-1 to NO3"(p<0.05 ). The results suggest that Aid injected intraperitoneally for 4 weeks can obviously increase the tissue CaN activity in the important organs in rat, especially in such target organs as heart, brain kidney and aorta which suggest that CaN may plays an important role on the damage of target organ of hypertension induced by aldosterone. Spironolactone can inhibitor the CaN activity by blocking the combination of aldosterone with its receptor, and this protect effect on heart may be carried out through the regulation of vessel active factor balance so tomake the relative predominant status of relaxation factors.Part II The role of CaN and its activity regulation in the animal model of cardiac hypertrophy produced by the injection intraperitoneally of aldosteroneTwenty-four Wistar rats were divided into three groups randomly: Three groups treated with aldosterone injected intraperitoneally were interfered with CsA ,spironolactone,and normal saline respectively while placebo with normal Salin. The concentrations of plasma Aldosterone (Ald), angiotensin II (Angll), endothelins (ET-1) and the ratio of left ventricular weight to body weight (LW/B W) as well as the activity of CaN in the cardiac tissue were measured. Half quantitative PCR was employed to determine the levels of ANF , -MHC and CaNA mRNA in cardiac tissue. The expression of CaN and NFAT3 in cardiac tissue were observed by immunohistochemical staining The results were that the plasma concentration of aldosterone increased obviously in aldosterone injected intraperitoneally group. Aldosterone injected intraperitone...