The neuroendocrinology of congestive heart failure.
The syndrome of heart failure is still imperfectly understood. It is defined as effort intolerance caused by heart disease, often with a neuroendocrine response that leads to fluid retention and promotes an adverse vicious circle. The cause of this response is generally thought to be a low blood pressure, leading to adrenergic and rennin-angiotensin activation. The result is increased peripheral vasoconstriction, which maintains the blood pressure while punishing the already failing myocardium by demanding more work against the increased afterload. The evolution of heart failure is traced out from an initial pressure or volume overload that initiates a series of growth signals to cause myocardial growth. Why the apparently well-compensated LV should degenerate into failure is not clear, but impaired coronary flow reserve and excess angiotensin II activity with fibrosis and apoptosis all probably play a role. The collagen matrix normally limits cardiac chamber expansion so that matrix remodeling under the influence of matrix metalloproteinases is required for the LV to enlarge in volume. Regarding the neuroendocrine responses, excess adrenergic activity promotes failure by myocardial membrane damage and calcium overload, and by increasing the myocardial oxygen demand and the afterload. Beta2- adrenergic stimulation may (unexpectedly) be anti-apoptotic and cardioprotective. Activation of the rennin-angiotensin system (RAS) is clearly very harmful, as shown by numerous studies in which inhibiting agents have reduced human mortality. Specific adverse consequences of RAS activation include (1) excessive peripheral vasoconstriction; (2) aldosterone-mediated sodium retention and myocardial fibrosis; (3) increased endothelial damage; and (4) excessive angiotensin II effects at intracellular sites. Other neuroendocrine changes are increased levels of endothelin and of cytokines such as tumour necrosis factor-alpha. Ergoreflexes from the ailing skeletal muscle may further promote adrenergic and RAS activation. Conversely, increased release of natriuretic peptides from the left heart is cardioprotective by limiting fluid retention and promoting vasodilation. Current therapies of heart failure are largely based on inhibition of the neuroendocrine response.
Opie
Lionel H
LH
Cape Heart Centre, Department of Medicine, University of Cape Town, South Africa.
D000804:Angiotensin II / Q000502:physiology; D017209:Apoptosis / Q000502:physiology; D009320:Atrial Natriuretic Factor / Q000502:physiology; D002118:Calcium / Q000502:physiology; D006332:Cardiomegaly / Q000503:physiopathology; D002395:Catecholamines; D016207:Cytokines / Q000502:physiology; D016232:Endothelins / Q000502:physiology; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D009452:Neuroendocrinology; D012084:Renin-Angiotensin System / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology*
D002395:Catecholamines; D016207:Cytokines; D016232:Endothelins; D000804:Angiotensin II; D009320:Atrial Natriuretic Factor; D002118:Calcium