Atrial Natriuretic Peptides [ANP] 20/01/2012

Atrial Natriuretic Peptides Atrial natriuretic peptide (ANP), atrial natriuretic factor (ANF), atrial natriuretic hormone (ANH), or atriopeptin, is a powerful vasodilator, and a protein (polypeptide) hormone secreted by heart muscle cells. It is involved in the homeostatic control of body water, sodium, potassium and fat (adipose tissue). It is released by muscle cells in the upper chambers (atria) of the heart (atrial myocytes) in response to high blood pressure. ANP acts to reduce the water, sodium and adipose loads on the circulatory system, thereby reducing blood pressure.1 31/12/2018

Learning Objectives Nature and biosynthesis Main effects Mechanism of action Therapeutic potential 31/12/2018

Atrial Natriuretic Peptides – 1) Nature and Biosynthesis Atrial cells have a specialised endocrine function in relation to the cardiovascular system They contain secretory granules, and store and release atrial natriuretic peptides (ANP) with powerful effects on the kidney and vascular system 31/12/2018

Two related natriuretic peptides (B and C) are found Release of ANP occurs during volume overload in response to stretching of the atria Two related natriuretic peptides (B and C) are found BNP is found in ventricular muscle CNP is found in vascular endothelium The plasma concentration of B-type natriuretic Peptide (BNP) is predictably increased in patients with heart failure and is increasingly used as an aid to diagnosis 31/12/2018

Atrial Natriuretic Peptides – 2) Main Effects To increase Na+ and water excretion by the kidney Relax vascular smooth muscle (except efferent arterioles of renal glomeruli) Increase vascular permeability Inhibit the release and/or actions of several hormones and mediators including aldosterone, angiotensin II, endothelin and antidiuretic hormone (ADH) 31/12/2018

Atrial Natriuretic Peptides – 3) Mechanism of Action ANPs exert their action by combining with membrane receptors (natriuretic peptide receptors, NPRs) which exist at least in two subtypes (A and B) Both NPR-A and NPR-B incorporate a catalytic guanylate cyclase moiety 31/12/2018

Atrial Natriuretic Peptides – Mechanism of Action ANP-receptor binding leads to increase cGMP (cyclic 3’5’-guanosine monophosphate) intracellular generation, same response as that produced by organic nitrates and endothelial-derived-NO (nitric oxide) 31/12/2018

Elsewhere ANP cause vasodilatation and reduce blood pressure However, interaction is through membrane-bound guanylate cyclase for ANP and soluble guanylate cyclase for organic nitrates and endothelial NO Renal glomerular arterioles are dilated by ANP but efferent arterioles are constricted increasing filtration pressure leading to increased glomerular filtration and enhanced Na+ excretion Elsewhere ANP cause vasodilatation and reduce blood pressure 31/12/2018

Atrial Natriuretic peptides – 4) Therapeutic Potential Vasodilations leads to decreased cardiac load (pre- and afterload) Increase Na+ and water excretion leads to reduction in preload For example: Nesiritide, a recombinant form of human B-type natriuretic peptide (BNP) approved by the FDA for the treatment of acute heart failure syndromes 31/12/2018

However, a pooled analysis of randomised controlled trials has suggested that it too may increase mortality 31/12/2018