Atrial Natriuretic Peptides [ANP] 9th of February, 2017

Atrial Natriuretic Peptides Overview...1/4 Cardiac natriuretic peptides are an important family of mediators Atrial Natriuretic Factor (ANF) is a 28 amino acid polypeptide hormone secreted mainly by the heart atria in response to atrial stretch ANF acts on the kidney to increase sodium excretion and GFR, to antagonize renal vasoconstriction, and to inhibit renin secretion 04/07/2018 JYS

Atrial Natriuretic Peptides Overview...2/4 Atrial natriuretic peptide (ANP), atrial natriuretic factor (ANF), atrial natriuretic hormone (ANH), Cardionatrine, Cardiodilatine (CDD) or atriopeptin, is a powerful vasodilator, and a protein (polypeptide) hormone secreted by heart muscle cells. 04/07/2018 JYS

Atrial Natriuretic Peptides Overview...3/4 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. 04/07/2018 JYS

Atrial Natriuretic Peptides Overview...4/4 ANP has exactly the opposite function of the aldosterone secreted by the zona glomerulosa in regard to its effect on sodium in the kidney –that is, aldosterone stimulates sodium retention and ANP generates sodium loss 04/07/2018 JYS

Atrial Natriuretic Peptides Learning Objectives At the end of the session, students should be able to understand and describe the following:- Nature and biosynthesis Main effects Mechanism of action Therapeutic potential 04/07/2018 JYS

Atrial Natriuretic Peptides – 1) Nature and Biosynthesis...1/3 Atrial cells have a specialised endocrine function in relation to the cardiovascular system They contain secretory granules, and store and release atrial natriuretic peptide (ANP) with powerful effects on the kidney and vascular system Release of ANP occurs during volume overload in response to stretching of the atria, and intravenous saline infusion is sufficient to stimulate its release. 04/07/2018 JYS

Atrial Natriuretic Peptides – 1) Nature and Biosynthesis...2/3 Two related natriuretic peptides (B and C) are found B-natriuretic peptide (BNP) is released from ventricular muscle and opposes ventricular fibrosis. 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. 04/07/2018 JYS

Atrial Natriuretic Peptides – 1) Nature and Biosynthesis...3/3 C-natriuretic peptide (CNP) is stored in vascular endothelium in addition to vascular actions influences development of long bones. 04/07/2018 JYS

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) 04/07/2018 JYS

Atrial Natriuretic Peptides – 3) Mechanism of Action...1/4 ANPs exert their action by combining with membrane receptors (natriuretic peptide receptors, NPRs) which exist at least in two subtypes designated (A and B) Both NPR-A and NPR-B incorporate a catalytic guanylate cyclase moiety (refer to How drugs act: molecular aspects) 04/07/2018 JYS

Atrial Natriuretic Peptides – Mechanism of Action...2/4 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) 04/07/2018 JYS

Atrial Natriuretic Peptides – Mechanism of Action...3/4 However, interaction is through membrane-bound guanylate cyclase for ANP and soluble guanylate cyclase for organic nitrates and endothelial NO Renal glomerular afferent arterioles are dilated by ANP but efferent arterioles are constricted, increasing filtration pressure leading to increased glomerular filtration and enhanced Na+ excretion 04/07/2018 JYS

Atrial Natriuretic Peptides – Mechanism of Action...4/4 Elsewhere, natriuretic peptides cause vasodilatation (vasorelaxation) and reduce blood pressure 04/07/2018 JYS

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 04/07/2018 JYS

However, a pooled analysis of randomised controlled trials has suggested that it too may increase mortality 04/07/2018 JYS

Reference Rang & Dale Pharmacology Textbook, 7th Ed, p 252-253 04/07/2018 JYS

THANK YOU FOR LISTENING! 04/07/2018 JYS