Thursday, June 25, 2009

Brain Natriuretic Peptides (BNP)

Brain natriuretic peptide (BNP) is a 32 amino acid polypeptide that is secreted by the ventricles of the heart in response to stretching of heart muscles1.

BNP was first discovered in porcine brain extracts based on its resemblance to atrial natriuretic peptide (a hormone secreted by mammalian atria) 1.

BNP belongs to the natriuretic family of peptides that contain three structurally related paracrine factors: Atrial, Brain and C-type natruirectic peptides2. Both atrial and brain natriuretic peptides are secreted in the atria and ventricles of the heart while C-type peptide is secreted in the bone2. BNP is co-secreted along with a 76 amino acid N-terminal fragment (NT-proBNP) which is biologically inactive3.

Structural Characteristics
BNP is a horseshoe-shaped 32 amino acid peptide that is held by a disulphide bridge formed between amino acids 10 and 264. It is produced by cleavage of large precursors- prepro and prohormones4.

Mode of action
BNP activates a transmembrane guanylyl cyclase, natriuretic peptide receptor-A (NPR-A). Activated NPR-A in turn produces the second messanger cGMP that triggers effectors that mediate its cardiac functions5,6.

BNP similar to ANP decreases systemic vascular resistance and central venous pressure resulting in a decrease in cardiac output and blood volume7. Both BNP and NT-proBNP levels in the blood are used for screening, diagnosis of acute congestive heart failure (CHF) and may be useful to establish prognosis in heart failure, as both markers are typically higher in patients with worse outcome8. The plasma concentrations of both BNP and NT-proBNP are also typically increased in patients with asymptomatic or symptomatic left ventricular dysfunction8.

BNP plays a very important role in prognostication of millions of diabetics9. It has an improtant role in prognostication of heart surgery patients10. It has been shown that combining BNP with other tools like ICG can improve early diagnosis of heart failure and advance prevention strategies11. BNP can be elevated in renal failure12. The BNP test is used as an aid in the diagnosis and assessment of severity of congestive heart failure (also referred to as heart failure)13.

1.Tetsuji S, Kenji K, Naoto M and Hisayuki M (1988), A new natriuretic peptide in porcine brain, Nature, 332, 78-81.
2.Potter LR, Yoder AR, Flora DR, Antos LK, Dickey DM (2009), Natruiretic peptides: their structures, receptors, physiologic functions and therapeutic applications, Handb Exp Pharmacol, 191, 341-66.
3.Bibbins-Domingo K, Gupta R, Na B, Wu AH, Schiller NB, Whooley MA (2007). "N-terminal fragment of the prohormone brain-type natriuretic peptide (NT-proBNP), cardiovascular events, and mortality in patients with stable coronary heart disease". JAMA 297 (2): 169–76.
4.Brandt I, Lambeir AM, Ketelsleger JM, Vanderheyden M, Scharpé S and Meest ID, (2006), Dipeptidyl-peptidase IV converts intact B-type natriuretic peptide into its des-SerPro form. Clin. Chem, 52(1): 82-87.
5.David G. Lowe (1992), Human natriuretic peptide receptor-A guanylyl cyclase is self-associated prior to hormone binding, Biochemistry, 31 (43), pp 10421–10425.
6.Jun S, Peter M. S and Harvey R. W, (2005), Differential Effects of cGMP Produced by Soluble and Particulate Guanylyl Cyclase on Mouse Ventricular Myocytes, Experimental Biology and Medicine 230:242-250.
7.Bhalla V, Willis S, Maisel AS (2004). "B-type natriuretic peptide: the level and the drug--partners in the diagnosis of congestive heart failure". Congest Heart Fail 10(1 Suppl 1): 3–27.
8.Atisha D, Bhalla MA, Morrison LK, Felicio L, Clopton P, Gardetto N, Kazanegra R, Chiu A, Maisel AS (2004). "A prospective study in search of an optimal B-natriuretic peptide level to screen patients for cardiac dysfunction". Am. Heart J. 148 (3): 518–23.
9.Bhalla MA, Chiang A, Epshteyn VA, Kazanegra R, Bhalla V, Clopton P, Krishnaswamy P, Morrison LK, Chiu A, Gardetto N, Mudaliar S, Edelman SV, Henry RR, Maisel AS (2004). "Prognostic role of B-type natriuretic peptide levels in patients with type 2 diabetes mellitus". J. Am. Coll. Cardiol. 44 (5): 1047–52.
10.Lee CY, Burnett JC Jr. (2007), Natruiteric peptides and therapeutic applications, Heart Fail Rev, 12 (2), 131-42
11.Castellanos LR, Bhalla V, Isakson S, Daniels LB, Bhalla MA, Lin JP, Clopton P, Gardetto N, Hoshino M, Chiu A, Fitzgerald R, Maisel AS (2009). "B-type natriuretic peptide and impedance cardiography at the time of routine echocardiography predict subsequent heart failure events". J. Card. Fail. 15 (1): 41–7.
12.Bhalla V, Maisel AS (June 2004). "B-type natriuretic peptide. A biomarker for all the right reasons". Ital Heart J 5 (6): 417–20.
13.Fitzgerald RL, Cremo R, Gardetto N, Chiu A, Clopton P, Bhalla V, Maisel AS (2005). "Effect of nesiritide in combination with standard therapy on serum concentrations of natriuretic peptides in patients admitted for decompensated congestive heart failure". Am. Heart J. 150 (3): 471–7.

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