Heart failure atrial natriuretic peptide

NESIRITIDE Nesiritide (natrecor), a recombinant form of human brain natriuretic peptide (BNP), is FDA-approved for treatment of dyspnea due to congestive heart failure. The natriuretic peptides—atrial natriuretic peptide (ANP), BNP, and C-type natriuretic peptide—are a family of endogenous hormones that possess potent natriuretic, diuretic, and vasodilator properties. BNP is secreted by ventricular cardiac myocytes in response to stretch circulating levels of BNP correlate with the severity of heart failure. In the setting of heart failure, the effects of BNP counteract the effects of Angll and NE by producing vasodilation, natriuresis, and diuresis. 

The vascular endothelium produces a number of substances that are released basally into the blood vessel wall to alter vascular smooth muscle tone. One such substance is endothelin (ET-1). Endothelin exerts its effects throughout the body, causing vasoconstriction as well as positive inotropic and chronotropic effects on the heart. The resulting increases in TPR and CO contribute to an increase in MAP. Synthesis of endothelin appears to be enhanced by many stimuli, including Ag II, vasopressin, and the mechanical stress of blood flow on the endothelium. Synthesis is inhibited by vasodilator substances such as prostacyclin, nitric oxide, and atrial natriuretic peptide. There is evidence that endothelin is involved with the pathophysiology of many cardiovascular diseases, including hypertension, heart failure, and myocardial infarction. Endothelin receptor antagonists are currently available for research use only. 

Tkacova R, Liu PP, Naughton MT, et al. Effect of continuous positive airway pressure on mitral regurgitant fraction and atrial natriuretic peptide in patients with heart failure. JAm Coll Cardiol. Sep 1997 30(3) 739-745. 

In the example of a-human atrial natriuretic peptide (ANP), found at increased plasma levels in patients with heart failure, Numata et al. [70] demonstrated how IPCR sensitivity accelerated conventional assay procedures. For individual treatment of the cardiac patients, a prompt detection of atrial distension by the presence of the ANP marker would be desirable. Common ANP tests, however, take 2-3 days for the quantification of plasma by radiometric or ELISA techniques. With sandwich IPCR, the assay time could be shortened to 5 hours. A good correlation between IPCR and radiometric detection was maintained, combined with an additional improvement of the detection limit to 2 ng/L ANP. The average level of ANP in plasma for 25 patients with heart failure was found to be 117 100 ng/L, significantly higher than the typical level of 20 14 ng/L for healthy subjects. 

Atrial natriuretic peptide has a beneficial local hormone effect on the heart, and, theoretically, agents that mimic or enhance its effects may be useful in heart failure, e.g. candoxatril. 

The natriuretic peptide family has three members, atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). ANP is stored mainly in the right atrium, whereas BNP is found mainly in the ventricles. Both are released in response to pressure or volume overload. CNP is found mainly in the brain and has very low plasma concentrations. ANP and BNP plasma concentrations are elevated in patients with heart failure and are thought to balance the effects of the RAA system by causing natriuresis, diuresis, vasodilation, decreased aldosterone release, decreased hypertrophy, and inhibition of the SNS and the RAA system. 

C. Clinical Role ANP has been studied for possible use in the treatment of congestive heart failure, but results have been mixed. BNP has showed some benefit in small studies in patients with heart failure. At present there are no clinically important products that act as agonists or antagonists at atrial natriuretic peptide receptors. 

C) Atrial natriuretic peptide increases cardiac contractility in congestive heart failure... 

D) Patients with heart failure usually have high plasma levels of atrial natriuretic peptide (ANP)... 

Numerous neuroendocrine biomarkers correlate with severity of cardiac dysfunction. Heart failure is associated with increase in peripheral vascular resistance due to increases in sympathetic tone, norepinephrine, renin, angiotensin II, arginine vasopressin, and endothelin-1. The increased venous pressure causes atrial distension that stimulates production and release of atrial and brain natriuretic peptides (ANP, BNP) from the atria and ventricles, respectively. ANP inhibits the renin-angiotensin-aldosterone system. In humans and mammals, BNP has been found to be an early biomarker of left ventricular hypertrophy developing with doxorubicin cardiotoxicity, congestive heart failure, or occult dilated cardiomyopathy (Erkus et al. 2006 Walker 2006 Oyama, Sisson, and Solter 2007). 

---