ANP (Atrial Natriuretic Peptide)

Atrial Natriuretic Peptide (ANP, also called atrial natriuretic factor, ANF) is a 28-amino acid peptide cardiac hormone secreted primarily by cardiac atrial cardiomyocytes in response to mechanical stretch caused by elevated atrial pressure and volume. It was discovered in 1981 by de Bold et al., who demonstrated that intravenous injection of atrial extracts in rats produced dramatic natriuresis — a finding that revealed the heart as an endocrine organ.

ANP is synthesized as a 151-amino acid precursor (pre-pro-ANP), stored in secretory granules in atrial cardiomyocytes as pro-ANP (108 amino acids), and cleaved to active ANP (28 amino acids) plus N-terminal pro-ANP upon secretion.

**Signaling mechanisms:** ANP binds NPR-A (Natriuretic Peptide Receptor A, also called GC-A), a receptor guanylyl cyclase, to generate intracellular cGMP. cGMP activates PKG (protein kinase G), which produces: 1. **Renal effects**: Increases glomerular filtration rate (afferent arteriole dilation, efferent arteriole constriction), inhibits Na+ reabsorption in the inner medullary collecting duct → natriuresis and diuresis 2. **Vascular effects**: Smooth muscle relaxation via PKG-mediated MLCK inhibition → vasodilation 3. **Adrenal effects**: Inhibits aldosterone synthesis and secretion from zona glomerulosa → further reduces sodium retention 4. **Cardiac effects**: Inhibits cardiac fibroblast proliferation and collagen production → anti-fibrotic (via cGMP/PKG) 5. **Sympathetic inhibition**: Reduces renin secretion and sympathetic nervous system activity centrally

**The natriuretic peptide family:** ANP (from atria) is the founding member. BNP (brain/B-type natriuretic peptide) is secreted primarily by ventricular cardiomyocytes under increased wall stress and is the basis for cardiac biomarkers NT-proBNP and BNP (elevated in heart failure). CNP (C-type natriuretic peptide) acts via NPR-B and has bone-anabolic and vascular smooth muscle effects.

ANP plasma levels are elevated in hypertension, heart failure, and renal disease, and serve as biomarkers of cardiac volume status. Research applications span heart failure physiology, kidney disease, cardiac fibrosis, pulmonary hypertension, and the RAAS counterregulation axis.