Brain mechanisms of sympathetic activation in heart failure: Roles of the renin-angiotensin system, nitric oxide and pro-inflammatory cytokines (Review)

Patients with chronic heart failure (CHF) have an insufficient perfusion to the peripheral tissues due to decreased cardiac output. The compensatory mechanisms are triggered even prior to the occurrence of clinical symptoms, which include activation of the sympathetic nervous system (SNS) and other neurohumoral factors. However, the long-term activation of the SNS contributes to progressive cardiac dysfunction and has toxic effects on the cardiomyocytes. The mechanisms leading to the activation of SNS include changes in peripheral baroreceptor and chemoreceptor reflexes and the abnormal regulation of sympathetic nerve activity (SNA) in the central nervous system (CNS). Recent studies have focused on the role of brain mechanisms in the regulation of SNA and the progression of CHF. The renin-angiotensin system, nitric oxide and pro-inflammatory cytokines were shown to be involved in the abnormal regulation of SNA in the CNS. The alteration of these neurohumoral factors during CHF influences the activity of neurons in the autonomic regions and finally increase the sympathetic outflow. The present review summarizes the brain mechanisms contributing to sympathoexcitation in CHF.