1. Date of download: 7/9/2016 Copyright © 2016 American Medical Association. All rights reserved. From: Role of the Natriuretic Peptide System in Cardiorenal Protection Arch Intern Med. 2003;163(22):2696-2704. doi:10.1001/archinte.163.22.2696 Normal physiology of natriuretic peptides. Atrial natriuretic peptide (ANP) is largely secreted by atrial myocytes, whereas brain natriuretic peptide (BNP) is chiefly the product of the ventricular myocytes, and C-type natriuretic peptide (CNP) is derived from vascular endothelial cells. All 3 peptides are produced in the brain. ADH indicates antidiuretic hormone; BP, blood pressure; EC, endothelial cells; GFR, glomerular filtration rate; NPCR, natriuretic peptide-C receptor; SNS, sympathetic nervous system; and VSMC, vascular smooth muscle cell. Figure Legend:

2. Date of download: 7/9/2016 Copyright © 2016 American Medical Association. All rights reserved. From: Role of the Natriuretic Peptide System in Cardiorenal Protection Arch Intern Med. 2003;163(22):2696-2704. doi:10.1001/archinte.163.22.2696 Mechanisms by which low-output heart failure leads to activation of neurohormonal vasoconstrictor systems (eg, sympathetic nervous system [SNS], renin-angiotensin-aldosterone system [RAAS], and vasopressin) and causes resistance to natriuretic peptide hormones (atrial natriuretic peptide [ANP] and brain natriuretic peptide [BNP]), impaired aldosterone escape, diminished distal tubular sodium and water delivery, and thus, renal and water excretion. These effects result in a vicious positive regulated feedback loop with further worsening of heart failure. Ang II indicates angiotensin II; NEP, neutral endopeptidase. Figure Legend:

3. Date of download: 7/9/2016 Copyright © 2016 American Medical Association. All rights reserved. From: Role of the Natriuretic Peptide System in Cardiorenal Protection Arch Intern Med. 2003;163(22):2696-2704. doi:10.1001/archinte.163.22.2696 Mechanism of action of vasopeptidase inhibitors. Dual inhibition of the angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) results in a shift in the balance resulting in inhibition of the renin-angiotensin-aldosterone system and activation of the physiologic actions of natriuretic peptides. ANP indicates atrial natriuretic peptide; AT1, antithrombin 1; BNP, brain natriuretic peptide; cGMP, cyclic guanosine monophosphate; CNP, C-type natriuretic peptide; GFR, glomerular filtration rate; NEP, neutral endopeptidase; NO, nitric oxide and PAI-1, plasminogen activator inhibitor 1. Figure Legend: