Biosynthesis, physiology and main diagnostic and therapeutic potentials of cardiac natriuretic peptides

Cardiac natriuretic peptides (NPs) is a family of peptide hormones, circulating in blood, originating from three prohormones: The atrial natriuretic peptide (ANP) prohormone synthesizes four active peptides (ANPs: Long-Acting Natriuretic Peptide, Vessel Dilator, Kaliuretic Peptide and ANP). B type natriuretic (BNP) and C type natriuretic (CNP) prohormones are cleaved in only one active peptide hormone each (BNP and CNP, respectively). ANPs and BNP bind to Natriuretic Peptide Receptor A (NPR-A) and CNP to NPR-B, which are transmembrane, guanylcyclase enzymes, in order to exert their biological effects. All NPs bind to a third receptor, NPR-C, which acts to clear them from the circulation. Activation of NPR-A mediates inhibition of renin-aldosterone system and natriuresis, as well as vasorelaxant, antifibrotic, anti-hypertrophic and anti-inflammatory and independent lipolytic effects. NPR-B activation is responsible for long bone growth. The properties of NPs to regulate plasma volume, through NPR-A activation, have been used for management of decompensated heart failure (HF) and acute renal failure. Human recombinant BNP (nesiritide) is commercially available for therapy of acute HF. Nesiritide improves hemodynamic profile and the clinical status of the patient. However, it may worsen renal function indicating a worse prognosis. Finally, plasma measurement of BNP has emerged as a useful, cost-effective biomarker for the diagnosis and prognosis of HF. However, other cardiovascular diseases as ischemia, arrhythmias and cardiac hypertrophy, as well as disorders of no cardiac origin, as sepsis and septic shock may cause elevated BNP levels.