Sympathetic nervous system
The sympathetic nervous system is activated in heart failure, via low and high pressure baroreceptors
, as an early compensatory mechanism which provides * inotropic support and maintains * cardiac output. Chronic sympathetic activation, however, has deleterious effects, causing a further * deterioration in cardiac function.
The earliest increase in sympathetic activity is detected in the heart
, and this seems to precede the increase in sympathetic outflow to skeletal muscle
and the kidneys
that is present in advanced heart failure.
Sustained sympathetic stimulation activates the @ renin-angiotensin-aldosterone system and other neurohormones, leading to * increased venous (PRE) and arterial (AFTER) tone (and greater preload and afterload respectively),* increased plasma noradrenaline concentrations, progressive * retention of salt and water, and oedema. Excessive sympathetic activity is also associated with cardiac myocyte apoptosis, hypertrophy, and focal myocardial necrosis.
In the long term, the ability of the myocardium to respond to chronic high concentrations of catecholamines is attenuated by a down regulation in β receptors, although this may be associated with baroreceptor dysfunction and a further increase in sympathetic activity.
Indeed, @ abnormalities of baroreceptor function are well documented in chronic heart failure, along with
reduced @ parasympathetic tone, leading to abnormal autonomic modulation of the sinus node
. Moreover, a reduction in heart rate
variability has consistently been observed in chronic heart failure, as a result of predominantly sympathetic and reduced vagal modulation of the sinus node, which may be a prognostic marker in patients with chronic heart failure.
There are three natriuretic peptides, of similar structure, and these exert a wide range of effects on the heart, kidneys, and central nervous system
Atrial natriuretic peptide (ANP)
is * released from the atria * in response to stretch, leading to * natriuresis and * vasodilatation.
In humans, brain natriuretic peptide (BNP)
is also released from the heart, predominantly from the ventricles, and its actions are similar to those of atrial natriuretic peptide. C-type natriuretic peptide
is limited to the vascular endothelium and central nervous system and has only limited effects on natriuresis and vasodilatation.
The atrial and brain natriuretic peptides * increase in response to volume expansion and pressure overload of the heart and act * as physiological antagonists to the effects of angiotensin II on vascular tone, aldosterone secretion, and renal-tubule sodium reabsorption. As the natriuretic peptides are important mediators, with increased circulating concentrations in patients with heart failure, interest has developed in both the diagnostic and prognostic potential of these peptides. Substantial interest has been expressed about the therapeutic potential of natriuretic peptides, particularly with the development of agents that inhibit the enzyme that metabolises atrial natriuretic peptide (neutral endopeptidase), and non-peptide agonists for the A and B receptors.
Other hormonal mechanisms in chronic heart failure
Antidiuretic hormone (vasopressin)
Patterns of neurohormonal activation and prognosishttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1128747/