Natriuretic peptide family

Atrial natriuretic peptide (ANP) mRNA has been found in many tissues, but most abundantly in the cardiac atria. Two other peptides derived from different precursor molecules encoded by different genes have been isolated. These are brain natriuretic peptide (BNP) and C-natriuretic peptide (CNP).

Confusingly, BNP is found in highest concentration in myocardial tissue, whereas CNP is found predominantly in the brain. ANP and BNP have mainly natriuretic and vasorelaxant properties, whereas CNP is not natriuretic. Natriuretic peptide receptors have been cloned for each of the peptides. Natriuretic peptides are cleaved by the enzyme neutral endopeptidase, although this is not the only mechanism of clearance. The affinity of the enzyme for BNP is much less than that for ANP and CNP.

Collectively, natriuretic peptides counterbalance the effects of the renin-angiotensin-aldosterone system. In response to volume expansion and pressure overload of the heart, plasma ANP and BNP concentrations increase, and one or both of them antagonize the effects of angiotensin II on the vascular tone, aldosterone secretion, renal tubular sodium reabsorption and vascular cell growth. Intravenous infusion of ANP is followed by a marked natriuresis with a rise in glomerular filtration rate and a fall in blood pressure.

Concentrations are elevated in heart failure and renal failure, and a possible therapeutic role for these actions in such conditions has been explored.

Currently, interest focuses mainly on the use of neutral endopeptidase inhibitors in the promotion of a salt and water diuresis. Plasma CNP concentrations change little with cardiac overload, and the main role of this peptide appears to be the regulation of vascular tone.