The Role of Natriuretic Peptides in the Pathophysiology and Treatment of Heart Failure

The Role of Natriuretic Peptides in the Pathophysiology and Treatment of Heart Failure

Jennifer L. Mathews (St. John Fisher College, USA) and Anne Schweighardt (St. John Fisher College, USA)
DOI: 10.4018/978-1-5225-2092-4.ch001
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Abstract

The pathophysiology of heart failure is due in part to compensatory mechanisms utilized to maintain cardiac output. Neurohormonal responses include activation of the renin-angiotensin-aldosterone and sympathetic nervous systems leading to vasoconstriction, increased blood volume through reabsorption of sodium and water, and increased myocardial contractility and heart rate. Prolonged activation of these systems often results in a maladaptive response and a further reduction in cardiac output (Colucci, 2015). Natriuretic peptides counterbalance the neurohormonal systems by antagonizing the actions of renin-angiotensin-aldosterone, promoting vasodilation and natriuresis. In hypervolemic states atrial myocytes are stretched resulting in the release of atrial natriuretic peptide (ANP). Ventricular cells secrete brain-type natriuretic peptide (BNP) in response to the high ventricular filling pressures (de Sa, 2008). The natriuretic peptides are degraded enzymatically by neprilysin. Plasma concentrations of ANP and BNP can be used as markers for the diagnosis of heart failure (Grewal, 2004). The kidneys also produce a natriuretic peptide, urodilatin, and new studies suggest a role for this peptide in the pathophysiology and treatment of heart failure (Anker, 2015). The natriuretic peptides can be targeted therapeutically for the treatment of heart failure. Nesiritide, a recombinant preparation of human B-type natriuretic peptide (BNP), is FDA approved and has been available for several years for treatment of acute decompensations of heart failure, but has received limited use due to cost and adverse effect profile. Ularatide, a synthetic analog of urodilatin, is currently in phase three clinical trials. In addition, the FDA has recently approved an angiotensin receptor blocker-neprilysin inhibitor that has shown mortality benefit.
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Pathophysiology Of Heart Failure

Heart failure begins with myocardial damage which can often be attributed to ischemic heart disease, hypertension or diabetes (Mozaffarian, 2016). The impaired myocardial fibers may be unable to contract (systolic HF) or relax (diastolic HF).

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