Atrial Natriuretic Peptide

Overview

Atrial natriuretic peptide (ANP) is a 28-amino acid peptide hormone secreted primarily by atrial cardiomyocytes in response to wall stretch caused by volume expansion. Discovered by de Bold in 1981, ANP was the first identified natriuretic peptide and established the heart as an endocrine organ. ANP is the prototype member of the natriuretic peptide family, which also includes B-type natriuretic peptide (BNP) and C-type natriuretic peptide (CNP).

Structure and Biosynthesis

ANP is derived from a 151-amino acid precursor (prepro-ANP) that is processed to the 126-residue pro-ANP (also termed gamma-ANP). Upon atrial stretch, pro-ANP is cleaved by corin, a transmembrane serine protease, releasing the active C-terminal 28-residue fragment. The mature peptide contains a conserved 17-residue disulfide-bridged ring structure formed between Cys7 and Cys23, which is essential for receptor binding. The linear C-terminal tail is required for full biological activity.

Receptor and Signaling

ANP binds preferentially to the natriuretic peptide receptor A (NPR-A), a particulate guanylyl cyclase. Receptor activation generates cyclic GMP (cGMP), which activates protein kinase G, promotes smooth muscle relaxation, and inhibits sodium reabsorption. NPR-A is expressed in the kidney, adrenal gland, vasculature, and brain. ANP also binds NPR-C, a clearance receptor that internalizes and degrades the peptide, and NPR-B with lower affinity. The natriuretic peptide system is counterregulated by the renin-angiotensin-aldosterone system.

Physiological Actions

ANP promotes renal sodium and water excretion (natriuresis and diuresis), reduces blood volume, and decreases blood pressure through direct vasodilation. It suppresses renin secretion from the juxtaglomerular cells, inhibits aldosterone synthesis from the adrenal cortex, and reduces sympathetic nervous system activity. ANP also inhibits cardiac fibroblast proliferation and reduces ventricular remodeling. In the CNS, ANP suppresses water and salt intake and modulates autonomic outflow.

Clinical Applications

ANP and its clinical analogue carperitide (synthetic human ANP) are used in Japan for acute heart failure management. ANP levels serve as diagnostic and prognostic biomarkers in heart failure. Nesiritide (recombinant BNP) exploits the same NPR-A pathway. Emerging research explores ANP-based therapies for pulmonary hypertension, acute kidney injury, and post-surgical fluid management. Genetic variants in the ANP gene are associated with hypertension susceptibility.