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Atrial natriuretic peptide and regulation of vascular function in hypertension and heart failure: implications for novel therapeutic strategies

Rubattu, Speranzaa,b; Calvieri, Camillaa; Pagliaro, Beniaminoa; Volpe, Massimoa,b

doi: 10.1097/HJH.0b013e32835ed5eb

Atrial natriuretic peptide (ANP) plays a pivotal role in modulation of vascular function and it is also involved in the pathophysiology of several cardiovascular diseases. We provide an updated overview of the current appraisal of ANP vascular effects in both animal models and humans. We describe the physiological implications of ANP vasomodulatory properties as well as the involvement of ANP, through its control of vascular function, in hypertension and heart failure. The principal molecular mechanisms underlying regulation of vascular tone, that is natriuretic peptide receptor type A/cyclic guanylate monophosphate, natriuretic peptide receptor type C, nitric oxide system, are discussed. We review the literature on therapeutic implications of ANP in hypertension and heart failure, examining the potential use of ANP analogues, neutral endopeptidase (NEP) inhibitors, ACE/NEP inhibitors, angiotensin receptor blocker (ARB)/NEP inhibitors, the new dual endothelin-converting enzyme (ECE)/NEP inhibitors and ANP-based gene therapy. The data discussed support the role of ANP in different pathological conditions through its vasomodulatory properties. They also indicate that ANP may represent an optimal therapeutic agent in cardiovascular diseases.

aDepartment of Cardiology, School of Medicine and Psychology, University Sapienza of Rome, Ospedale S. Andrea, Rome

bIRCCS Neuromed, Pozzilli (Isernia), Italy

Correspondence to Massimo Volpe, MD, Chief of the Department of Cardiology, School of Medicine and Psychology, Sapienza University of Rome, Sant’Andrea Hospital, Rome, Italy. Tel: +39 06 3377 5654; fax: +39 06 3377 5061; e-mail:

Abbreviations: ACE, angiotensin-converting enzyme; ANP, atrial natriuretic peptide; cGMP, cyclic guanylate monophosphate; CNP, C-type natriuretic peptide; ECE, endothelin-converting enzyme; ET-1, endothelin; ETA, endothelin receptor type A; ETB, endothelin receptor type B; NEP, neutral endopeptidase; NPR-A, natriuretic peptide receptor type A; NPR-B, natriuretic peptide receptor type B; NPR-C, natriuretic peptide receptor type C; pGC, particulate guanylyl cyclase

Received 16 October, 2012

Revised 28 November, 2012

Accepted 10 January, 2013

© 2013 Lippincott Williams & Wilkins, Inc.