brain natriuretic peptide

BNP is synthesized as a prepro-hormone (preproBNP) that is cleaved to proBNP, which is then split into biologically active BNP and inactive NT-proBNP in equimolar amounts upon release into circulation. It is released mainly by ventricular cardiomyocytes in response to increased myocardial wall stretch/stress, as seen in volume or pressure overload states like heart failure.

Mechanism of action: BNP binds natriuretic peptide receptor-A (NPR-A), activating guanylate cyclase to increase cGMP, leading to: (1) vasodilation of arterioles and veins (decreasing preload/afterload), (2) natriuresis and diuresis via increased GFR and decreased sodium reabsorption in the collecting duct, (3) inhibition of renin release and aldosterone secretion, and (4) inhibition of the sympathetic nervous system. Overall, BNP acts as a counter-regulatory hormone to the RAAS and sympathetic systems to reduce blood pressure, blood volume, and cardiac workload.

Clinical significance: BNP and NT-proBNP levels are used to diagnose acute decompensated heart failure, especially in the setting of dyspnea of unclear etiology (distinguishing cardiac vs. pulmonary causes). Levels correlate with severity of heart failure and are used for prognosis and monitoring treatment response. BNP <100 pg/mL makes heart failure unlikely; higher levels support the diagnosis. Note: NT-proBNP has a longer half-life and is less affected by short-term therapies like sacubitril/valsartan (a neprilysin inhibitor that would falsely elevate BNP levels since neprilysin normally degrades BNP).

Other considerations: BNP can be elevated in renal failure (reduced clearance), obesity is associated with falsely low levels, and atrial fibrillation, pulmonary embolism, and sepsis can also increase levels independent of heart failure. Recombinant BNP (nesiritide) has been used therapeutically in acute decompensated heart failure, though its clinical benefit is debated.