Activation of the neuroendocrine response in heart failure: Adaptive or maladaptive process?

Abstract

Congestive heart failure is a clinical syndrome in which the capacity of the heart to maintain cardiac output is impaired. As a consequence, blood pressure is threatened and endocrine and paracrine mechanisms are activated to preserve circulatory homeostasis and to maintain blood pressure. At terminal stages, a complex multiorgan syndrome develops with severe pump failure, intense systemic vasoconstriction, and avid water and sodium retention. Increasing evidence points to humoral circulating or locally synthesized substances as one of the causes of the terminal consequences of heart failure. Therefore, the hypothesis that the syndrome of heart failure is, at least in part, a humoral disease has developed and is obtaining scientific credibility. Consequently, the neuroendocrine response to heart failure is no longer viewed as a compensatory beneficial mechanism. Instead, we have learned through the years that pharmacological treatment aimed at reducing the effect of the neuroendocrine response is indeed clinically and prognostically advantageous for the patient.

Molecular and cellular mechanisms of cardiotoxicity.

“…BNP, is associated with numerous detrimental biological effects that eventually lead to cardiac failure by way of myocyte dysfunction, apoptosis, and cell loss (99). For instance, the ANP gene is expressed in both atrium and ventricle during embryonic development, but its expression is downregulated in the ventricle shortly after birth, leaving the atrium as the primary site of ANP synthesis within the mature myocardium (100).…”

“…For instance, the ANP gene is expressed in both atrium and ventricle during embryonic development, but its expression is downregulated in the ventricle shortly after birth, leaving the atrium as the primary site of ANP synthesis within the mature myocardium (100). During myocardial pathologic remodeling, reexpression of ANP in myocytes of the left ventricle takes place (99)(100)(101). Recent studies have demonstrated that ANP is a factor responsible for myocardial apoptosis (49,102).…”

Chronic Heart Failure- Potential for Pharmacological Intervention

“…Neuroendocrine activity occurs via sympathetic and renin angiotensin system, resulting in an increased level of norepinephrine and angiotensin II. Catecholamines and angiotensin II cause a direct increase in the release of von Willebrand factor [48,49,50].…”

β-blocker in Heart failure with reduced ejection fraction: A review

“…14,15 This compensatory mechanism may improve contractility and provide hemodynamic support in short term. However, chronic adrenergic stimulation can be deleterious because it may cause myocardial damage due to changes in left ventricular remodeling, loss of myocardial cells and abnormal gene expression.…”