Atrial Natriuretic Factor

Atrial natriuretic factor (ANF) can be defined as a natriuretic peptide hormone in the human body that is secreted from the atria.  The atria of the heart are crucial regulators of blood pressure and volume. The atrial natriuretic factor’s principal purpose is to reduce the volume of expanded extracellular fluid (ECF) by boosting salt excretion from the kidneys. 

Adolfo José de Bold originally reported the identification of a natriuretic factor in 1981, when rat atrial extracts were found to have a chemical that raised salt and urine production in the kidney. ANF is also known as Atrial Natriuretic Peptide (ANP).

Structure of Atrial Natriuretic Factor

The atrial natriuretic factor is a 28-amino-acid peptide with a 17-amino-acid ring in the middle. A disulfide link connects two cysteine residues at positions 7 and 23 to produce the ring. 

Atrial natriuretic factor shares an amino acid ring structure with BNF (brain natriuretic factor) and CNF (C-type natriuretic factor). It is one of nine structurally related natriuretic hormones, seven of which are produced by the heart.

 Types of Atrial Natriuretic Factor Receptors

There are three types of atrial natriuretic peptide receptors on which natriuretic factors operate. They’re all cell surface receptors with different names. They are:

• Natriuretic peptide receptor-A or NPR1
• Natriuretic peptide receptor-B or NPR2
• Natriuretic peptide clearance receptor or NPR3

Role of Atrial Natriuretic Factor

• ANF operates on the kidney to promote salt excretion and Glomerular Filtration Rate (GFR), limit renin secretion, and counteract renal vasoconstriction.
• ANF inhibits vasoconstriction in the cardiovascular system and moves fluid from the intravascular to the interstitial compartment.
• The natriuretic response to acute and chronic volume overload is heavily influenced by ANF. The ability of ANF to move fluid out of the circulatory system is one of its most notable features.
• ANF is a potent inhibitor of aldosterone synthesis in the adrenal gland.
• The ability of ANF to move fluid from the vascular to the interstitial compartment functions as a buffer, preventing excessive plasma volume expansion in response to an increase in total extracellular fluid volume.
• When salt excretion is threatened by a reduction in the number of nephrons, ANF acts as a physiological regulator of Glomerular Filtration Rate (GFR), mediating nephron hyperfiltration and natriuresis.

Cause of Atrial Natriuretic Factor Secretion

The 28-amino-acid polypeptide hormone atrial natriuretic factor (ANF) is released primarily by the heart atria in response to atrial stretch. Atrial natriuretic factor (ANF)  is produced in response to the following stimuli:

• The atrial wall is stretched by atrial volume receptors.
• Sympathetic activation of adrenoceptors is increased.
• Increased sodium concentration (hypernatremia), albeit this, is not the direct cause of increased ANP secretion.
• Presence of a powerful vasoconstrictor, endothelin

Physiological effects of Atrial Natriuretic Factor (ANF)

1.     Renal- ANF stimulates sodium and water excretion in the kidneys. It happens in the following way:

• The main location of ANP control of sodium excretion is the medullary collecting duct.
• The glomerular filtration rate and permeability are both increased by ANF. ANF dilates the afferent arteriole directly, counteracting the afferent arteriole’s vasoconstriction caused by norepinephrine.
• Increases blood flow through the vasa recta, allowing the solutes (NaCl and urea) to be washed out of the medullary interstitium.
• It reduces sodium reabsorption in the nephron’s thick ascending limb and cortical collecting duct.
• It prevents the formation of angiotensin and aldosterone by suppressing renin secretion.
• It suppresses the sympathetic nervous system of the kidneys. 

2.     Adrenal- Reduces aldosterone secretion by the adrenal cortex’s zona glomerulosa.

3.     Vascular- Relaxes the smooth muscle of the circulatory system in arterioles and venules by:

• Increase  in vascular smooth muscle mediated by membrane receptors
• Catecholamines’ actions are inhibited. 
• Encourages uterine spiral artery remodelling, which is critical for reducing pregnancy-induced hypertension.

4.     Cardiac- 

• Atrial Natriuretic Factor prevents myocardial hypertrophy and fibrosis in heart failure. Fibrosis is slowed by preventing fibroblasts from entering and multiplying in the heart tissue, as well as reducing inflammation.
• Atrial Natriuretic Factor inhibits hypertrophy by decreasing norepinephrine-induced calcium influx.
• The phenotype is saved when NPRA is re-expressed.

5.     Immune system – Several immune cells manufacture ANF locally. ANF has been demonstrated to have cytoprotective effects and regulate various aspects of the innate and adaptive immune systems.

• Atrial Natriuretic Factor affects innate immunity by increasing defence against extracellular microorganisms while also suppressing the production of pro-inflammatory signals and adhesion molecule expression.
• In myocardial, vascular smooth, endothelial, hepatocytes, and tumour cells, ANP has been shown to have cytoprotective properties.

6.     Adipose tissue-

• Increases release of free fatty acids from adipose tissue. In humans, I.V. Infusion of ANF increases plasma concentrations of glycerol and unsaturated fatty acids.
• Increases intracellular cGMP levels, which causes a hormone-sensitive lipase and perilipin to be phosphorylated. 

Conclusion

The excitement around the discovery of atrial natriuretic factor stemmed in part from the fact that its physiological job appeared to be straightforward. Because of ANF’s strong natriuretic properties and its position in the cardiac atria, it’s possible that it’s responsible for the increase in salt and water excretion that occurs when atrial chamber pressure rises. 

ANP production has been detected in tissues other than the cardiac atria, and receptor binding studies have revealed organs other than the kidneys as target organs. As a result, it’s safe to assume that our understanding of ANP’s physiological role will need to evolve in the coming years.