Role of neuroendocrine mechanisms in the pathogenesis of heart failure

Abstract

In chronic heart failure, neurohumoral mechanisms play an important role in the regulation of cardiac performance by direct influences on systolic and diastolic function of the myocardium, and indirectly, by modulation of pre- and afterload. Important vasoconstrictor, fluid- and sodium-retaining factors are the renin-angiotensin-aldosterone system, sympathetic nerve activity, and vasopressin; vasodilator, volume, and sodium-eliminating factors are atrial natriuretic peptide, vasodilator prostaglandins like prostacyclin and prostaglandin E2, dopamine, bradykinin, and possibly, endothelial derived relaxing factor (EDRF). There is evidence from experimental and clinical studies that the sympathetic nerve activity is stimulated in the early phase of the disease, as well as is the secretion of atrial natriuretic peptide which increases in relation to a rise in preload. In early or mild heart failure, atrial natriuretic peptide suppresses the activity of the renin-angiotensin-aldosterone system, which may prevent an increase in peripheral vascular resistance and preserve renal blood flow. In more severe heart failure, the renin-angiotensin-aldosterone system is activated, leading to an increase of peripheral and renal vascular resistance and fluid and sodium retention. This is associated with an increased production of vasodilator prostaglandins. In severe heart failure, mostly in connection with hyponatremia, a nonosmolar, inappropriately high secretion of vasopressin can be demonstrated. These findings suggest that early interventions in order to suppress unfavorable neurohumoral mechanisms or to support protective factors like atrial natriuretic peptide may be of particular importance in the treatment of congestive heart failure with the aim of a retardation of the progression of the disease, which would result in an improvement of survival.