Chronic heart failure: a disease of the brain

• Published in: Heart failure reviews 2019-03, Vol.24 (2), p.301-307
• Main Authors: Singh, Ram B., Hristova, Krasimira, Fedacko, Jan, El-Kilany, Galal, Cornelissen, Germaine
• Format: Article
• Language: English
• Subjects: Adaptations; Adrenal glands; Aldosterone; Angiotensin; Angiotensin II; Angiotensin II - blood; Angiotensin Receptor Antagonists - administration & dosage; Animals; Area postrema; Autonomic nervous system; Baroreceptors; Baroreflex - drug effects; Baroreflex - physiology; Brain - physiopathology; Cardiology; Cardiomegaly - physiopathology; Central nervous system; Chemoreception (internal); Chronic Disease; Coronary artery disease; Heart - physiopathology; Heart diseases; Heart failure; Heart Failure - physiopathology; Humans; Inflammation - metabolism; Medicine; Medicine & Public Health; Medulla oblongata; Muscle contraction; Natriuretic Peptide, Brain - metabolism; Nerve endings; Neuroimmunomodulation - drug effects; Neuroimmunomodulation - physiology; Norepinephrine; Norepinephrine - metabolism; Oxidative stress; Oxidative Stress - physiology; Parasympathetic nervous system; Paraventricular Hypothalamic Nucleus - drug effects; Paraventricular Hypothalamic Nucleus - physiology; Paraventricular nucleus; Peptide Fragments - metabolism; Reflexes; Renin; Renin-Angiotensin System - physiology; Sensory neurons; Subfornical organ; Sympathetic Nervous System - drug effects; Sympathetic Nervous System - physiopathology; Vagus Nerve Stimulation - adverse effects; Vagus Nerve Stimulation - methods
• ISSN: 1382-4147; 1573-7322
• DOI: 10.1007/s10741-018-9747-3

The underlying mechanism for clinical and biochemical manifestations of chronic heart failure (HF) may be due in part to neurohumoral adaptations, such as activation of the renin-angiotensin-aldosterone and sympathetic nervous systems in the periphery and the brain. Internet search and discussion with colleagues are the methods for this study. Since chronic HF is associated with autonomic imbalance with increased sympathetic nerve activity and a withdrawal of parasympathetic activity, it may be considered a brain disease. This phenomenon may be the result of an increased systemic and cerebral angiotensin II signaling because plasma angiotensin II is increased in humans and animals with chronic HF. The increase in angiotensin II signaling enhances sympathetic nerve activity through actions on both central and peripheral sites during chronic HF. Activation of angiotensin II signaling in different brain sites such as the paraventricular nucleus (PVN), rostral ventrolateral medulla (RVLM), and area postrema (AP) may increase the release of norepinephrine, oxidative stress, and inflammation leading to increased cardiac contractility. It is possible that blocking angiotensin II type 1 receptors decreases sympathetic nerve activity and cardiac sympathetic afferent reflex when therapy is administered to the PVN. The administration of an angiotensin receptor blocker by injection into the AP activates the sympatho-inhibitory baroreflex indicating that receptor blockers act by increasing parasympathetic activity. In chronic HF, in peripheral regions, angiotensin II elevates both norepinephrine release and synthesis and inhibits norepinephrine uptake at nerve endings, which may contribute to the increase in sympathetic nerve activity. Increased circulating angiotensin II during chronic HF may enhance the sympatho-excitatory chemoreflex and inhibit the sympatho-inhibitory baroreflex resulting in worsening of HF. Increased circulating angiotensin II signaling can directly act on the central nervous system via the subfornical organ and the AP to increase sympathetic outflow resulting in to neurohumoral dysfunction, resulting in to heart failure.