BNP

BNP binds NPR-A (the same receptor as ANP) with similar affinity, activating intrinsic guanylyl cyclase activity and elevating intracellular cGMP. PKG activation mediates vasodilation of arterial and venous beds, reducing both preload and afterload. In the kidney, BNP increases GFR and inhibits sodium reabsorption in the collecting duct, promoting natriuresis. BNP also suppresses renin and aldosterone, further reducing sodium retention and volume expansion.

The breakthrough heart failure drug sacubitril/valsartan (Entresto) works by preventing neprilysin-mediated degradation of BNP and ANP, augmenting endogenous natriuretic peptide signaling while simultaneously blocking AT1R with valsartan. This combination produced 20% mortality reduction versus enalapril in PARADIGM-HF, the largest advance in heart failure pharmacotherapy in decades, and validates enhancing BNP signaling as a therapeutic strategy.

BNP and NT-proBNP are the gold-standard biomarkers for heart failure diagnosis, guiding treatment decisions and monitoring. A BNP above 100 pg/mL (or NT-proBNP above 300 pg/mL) strongly supports heart failure in dyspneic patients. Serial BNP measurement guides diuretic titration and identifies patients at high risk for 30-day readmission or death.

Nesiritide (recombinant BNP) received FDA approval for acute decompensated heart failure based on rapid symptom relief and hemodynamic improvement in early trials. The ASCEND-HF trial (7141 patients) showed modest dyspnea relief but no 30-day mortality benefit, and controversy over renal effects limited use. Nesiritide is now used selectively in patients with severe dyspnea requiring rapid hemodynamic improvement.

PARADIGM-HF demonstrated sacubitril/valsartan superiority over enalapril with 20% reduction in cardiovascular death and heart failure hospitalization in HFrEF patients. This drug, by preventing natriuretic peptide degradation, validates amplifying endogenous BNP/ANP signaling as a core therapeutic strategy in heart failure.