Atrial Natriuretic Factor: History, Structure, Production and Effects

Atrial Natriuretic Factor, abbreviated as ANF, is a peptide hormone secreted by the cardiac atria in humans. It is also named the Atrial Natriuretic Peptide (ANP). It is secreted by the cardiac muscles in the atrial walls of the heart. The hormone works on reducing blood volume in response to the stretching of the atrial wall corresponding to an increase in the blood volume in the atria. It has associated effects following this volume reduction. These secondary effects include reduced extracellular fluid (ECF), a decrease in blood pressure, and increased potassium content. There are specific regulatory mechanisms to counter these changes in the body.

ANF Hormone

The ANF (ANP) hormone gets secreted by the action of the NPPA gene in humans. It increases sodium excretion from the body through the renal fluid (urine), causing reduced extracellular fluid volume and associated secondary effects. ANP is a cardiac signaling molecule acting as a diuretic that inhibits the reabsorption of sodium by the kidneys. The importance of this hormone lies in the fact that it is vital in cardiac development. The malfunctioning of this gene can lead to cardiac problems due to changes in ANP levels. ANP is found in amphibians, mammals, and bony fishes. It is absent in cartilaginous fishes, reptiles, and birds.

History

A cardiovascular researcher, Adolfo José be Bold, first identified the natriuretic factor in rats in 1981. The atrial extracts of rats show a factor that increased the water and salt excretion. This factor was successfully separated and purified from the heart tissue and was named the Atrial Natriuretic Factor (ANF).

Structure And Production

ANP is a peptide hormone with 28 amino acid peptides and a 17 amino acid ring in the middle. It is one of the nine in the family of structurally similar hormones of natriuretic nature, and seven are of atrial origin.

ANP is initially synthesized as an inactive hormone (preprohormone - a precursor to peptide hormone). The coding of the hormone is by the NPPA gene on chromosome 1. The cleavage of the signal peptide, a sequence of 25 amino acids, forms proANP (126 amino acid peptide) and is stored in the atrial granules.

On the stimulation of the atrial walls, proANP gets converted to a 28 amino acid mature ANP. It can happen due to several reasons.

• An increased sodium concentration is known as hypernatremia.

• The stretching of atrial walls.

• Increase in Endothelin, a vasoconstrictor.

Actions Of ANF

• Kidney - It increases the excretion of water and sodium by increasing the glomerular filtration rate. The increased blood flow through the vasa recta removes the sodium solutes. The reduced sodium reabsorption by the ascending limb of nephrons and deactivation of the renal SNS (Sympathetic Nervous System) also adds to the effect. The hormones like aldosterone (which promotes sodium conservation) and angiotensin (which increases blood pressure by blood vessel constriction) are inhibited as ANPs inhibit renin secretion. All of these result in decreased sodium reabsorption.

• Cardiac effect - ANP helps to inhibit cardiac hypertrophy (thickening of heart muscles, which makes it harder for the heart to pump blood) by inhibiting calcium influx. Fibrosis is also prevented by decreasing inflammation and preventing fibroblasts from entering and replicating in the heart tissues.

• Adipose tissue - It releases the fatty acids stored in adipose tissues. The infusion of ANP can increase glycerol plasma concentrations in humans.

• Immune system - ANP produced by the immune cells helps to raise the defence. It acts against the extracellular microbes and gives cytoprotective effects (protection against harmful agents).

ANF As Biomarker

• ANP can be used as a biomarker in various cardiovascular disorders, including stroke, heart failure, and myocardial infarction.

• MRproANP (Mid-Regional Pro-Atrial Natriuretic Peptide) is a precursor of ANP that is an extremely sensitive biomarker in heart failure. Its levels above 120 pmol/L indicate possible heart failure.