Atrial natriuretic factor

Atrial natriuretic factor (ANF), atrial natriuretic peptide (ANP) or atriopeptin, is a polypeptide hormone involved in the homeostatic control of body water,sodium, and adiposity. It is released by atrial myocytes, cells in the atria of the heart, in response to signals of raised blood pressure and acts to reduce the water, sodium and adipose loads on the circulatory system, thereby returning blood pressure to more normal levels.

Structure
ANP is a 28 amino acid peptide with a 17 AA ring, and is closely related to BNP (Brain Natriuretic Peptide, but produced largely in the heart) and CNP (C-type Natriuretic Peptide) which all share the same amino acid ring. ANP was discovered in 1981 by a team in Ottawa led by Mercedes Kuroski de Bold after they made the seminal observation that injection of atrial (but not ventricular) tissue extracts into rats caused copious natriuresis.

Production
ANP is produced, stored and released by cells present in the atria of the heart, atrial myocytes. It is released in response to a variety of signals, the signals, present when the subject is hypervolaemic, exercised or calorically restricted.

It is secreted in response to:
 * Atrial distention, stretching
 * Sympathetic stimulation of β-adrenoceptors
 * Raised sodium concentration
 * Angiotensin-II
 * Endothelin, a potent vasoconstrictor

Causes of stretching include high extracellular fluid volume, high blood volume, and atrial fibrillation. Notably, it is secreted in response to immersion of the body in water, which causes an atrial stretch due to altered distribution of intravascular fluid. It has been shown that in horses, it is also released in response to exercise.

Receptors
There are three distinct receptors identified so far in mammals, natriuretic peptide receptors A, B and C (NPRA or, NPRB or and NPRAC or ).

NPRA and NPRB are linked to guanylyl cyclases, while NPRAC is G-protein linked and furthermore is a "clearance receptor" which acts to internalise and destroy the ligand.

Physiological effects
The overall effects of ANP release are a reduction in blood volume and therefore central venous pressure, cardiac output, and arterial blood pressure. It increases renal sodium secretion and excretion. It also increases lipolysis.

The overall effect of which is to counter the blood pressure-raising effects of the renin-angiotensin system.

Renal

 * Dilates the afferent glomerular arteriole, constricts the efferent glomerular arteriole, and relaxes the mesangial cells. This increases the glomerular filtration rate, resulting in greater excretion of sodium and water.


 * Decreases sodium resorption in the renal distal convoluted tubule and cortical collecting duct.


 * Inhibits renin secretion.

Vascular

 * Relaxes vascular smooth muscle in arterioles and venules by:
 * Receptor-mediated elevation of vascular smooth muscle cGMP
 * Inhibition of the effects of catecholamines

Adrenal

 * Reduces aldosterone secretion by the adrenal cortex.

Adipose Tissue

 * Increases the release of free fatty acids from adipose tissue. Plasma concentrations of glycerol and nonesterified fatty acids are increased by i.v. infusion of ANP in humans.
 * Activates adipocyte plasma membrane type A guanylyl cyclase receptors NPR-A
 * Increases intracellular guanosine 3',5'-cyclic monophosphate cyclic GMP levels that induce the phosphorylation of a hormone-sensitive lipase and perilipin A via the activation of a cGMP dependent protein kinase-I cGK-I
 * Does not modulate cAMP production or PKA activity

Degradation
Degradation of ANP is needed for its actions to be stopped. It is broken down by an enzyme, neutral endopeptidase (NEP). Recently inhibitors of NEP have been developed, although have not yet been licenced, proving to be beneficial in congestive heart disease.

Other natriuretic factors
In addition to the mammalian natriuretic factors (ANP, BNP, CNP), two other peptides have been isolated. Tervonen (1998) described a salmon natriuretic factor (Salmon cardiac peptide) with a similar structure and properties and Dendroaspis Natriuretic Peptide (DNP) was discovered in the venom of the green mamba by Schweitz et al. (1992).