| In 1990s, our understanding of heart failure and the ability to manage it changed a lot from what it has been in 1950s. The principle goal of therapy was rather to improve survival than to alleviate symptoms and correct hemodynamic abnormalities.Left ventricular remodeling plays a key role in the development of heart failure and initially represent an adaptive response to hemodynamic overload. However, it is generally accepted that left ventricular remodeling decreased the cardiac performance and became maladaptive when the process of heart failure developed. It is one of the most critical risk factors of heart failure. Therefore, for the treatment of heart failure it is important to understand the mechanism of left ventricular remodeling and to establish effective pharmaceutical interventions to reverse it.It is now clear that in the condition of left ventricular remodeling, a number of cytokines and neurohormonal systems, notably the adrenergic nervous system (ANS) and renin-angiotensin-aldosterone system (RAS) are activated. No matter which biological response system has its opposite side. The existence of the systems to oppose the activation of RAS and ANS seemed important in the development of left ventricularremodeling. For this reason, to reverse left ventricular remodeling is not only to inhibit the activity of RAS and ANS, but also to activate the opposite system of them. It is the same in the management of heart failure. Angiotensin converting enzyme inhibitors (ACEI) and beta-blockers (BB) are used to inhibit RAS and ANS activity, on the other hand, neutral endopeptidase (NEP) inhibitors are used in the concept to oppose the activity of angiotensin II.Left ventricular remodeling changes the geometry of the heart and the gene expression as well. The fetal gene program induced by the activation of neurohormonal factors alters the structural proteins of the sarcomere, leading to worsening of cardiac contractility. So the therapy of heart failure was claimed to reverse the fetal program of gene expression.Therefore, we design the intervention studies on ACEI and BB in heart failure focus on the role of left ventricular remodeling, and investigate angiotensin n, B-type natriuretic peptide (BNP) and the expression of myosin heavy chain (MHC) in heart failure patients and spontaneously hypertensive rats (SHR).Our results show: 1. Plasma angiotensin II and BNP elevate in heart failure patients and cardiac hypertrophied SHR, the elevation reflect the severity of heart failure and left ventricular hypertrophy. 2. The elevation of left ventricle angiotensin n and BNP is parallel to the severity of leftventricular hypertrophy in SHR. 3. Plasma angiotensin II does not reduce after ACEI treatment, while plasma BNP decrease significantly. BB therapy reduces both plasma angiotensin and BNP. 4. The amount of total MHC gene expression in the hypertrophied myocardium decreased and the ratio of 3 / a -MHC increased, suggest a -MHC gene expression was reduced while 0 -MHC was elevated in hypertrophied myocardium. ACEI and BB intervention normalized the ratio of (3 / a -MHC, indicate that they can reverse the molecular remodeling in cardiac hypertrophy.ACEI intervention in heart failure patients and cardiac hypertrophied rats do not decrease the plasma angiotensin II, while the concentration of plasma BNP decrease significantly. The reason may be related to non-ACE pathways in the production of angiotensin II. BB inhibits the activation of RAS at a fundamental level and decreases the angiotensin II concentration. The biological actions of BNP antagonize the RAS. We found that BNP increased when angiotensin II increased, and decreased when the activity of RAS was inhibited. From this point of view, BNP may be regarded as a marker of RAS activity or the response to ACEI and BB therapy. The detection of BNP may have important clinical implications in the treatment of heart failure.The result of MHC gene expression indicates that a -MHC was decreased and |3 -MHC was increased in hypertrophied myoc...
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