Atrial natriuretic peptide and regulation of vascular function in hypertension and heart failure

Abstract

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.

Effects of Sacubitril/Valsartan (LCZ696) on Natriuresis, Diuresis, Blood Pressures, and NT-proBNP in Salt-Sensitive Hypertension

“…[9][10][11] Another cGMP-dependent mechanism that may explain the apparent dissociation of short-term effects of sacubitril/ valsartan on natriuresis and diuresis but sustained significant BP reduction is related to the vasodilatory effects of ANP. 15 ANP exhibits a potent vasodilatory effect on large arteries through the natriuretic peptide A receptor/cGMP pathway in both animal models and in humans. [32][33][34] The vasodilatory effects, along with initial natriuresis, could reset sodium and water homeostasis and prevent sustained natriuresis and diuresis.…”

“…Among multiple pathophysiological mechanisms, a relative deficiency of atrial natriuretic peptide (ANP) is considered to result in sodium retention and a suboptimal vasodilatory response to sodium loading observed in patients with SSH. [12][13][14][15] The renin-angiotensin-aldosterone system (RAAS) also plays a role in the pathogenesis of SSH by modulating renal sodium reabsorption. 16 Therefore, enhancing the activity of natriuretic peptides along with inhibition of the RAAS may be an effective, pathogenesis-oriented, and safe alternative to improve BP control in patients with SSH.…”

Constructive Development of Aging

“…Natriuretic peptides are generally present in significantly higher levels during aging [16]. Natriuretic peptides have many potentially beneficial properties for heart failure patients, including opposition to vasoconstriction, sodium retention and antidiuretic effects [17,18]. A number of therapeutic approaches to increase atrial natriouretic peptides (ANP) are currently being investigated, including the use ANP analogues such as carpetide and the use of several inhibitors of neutral peptidase inhibitors which block breakdown of ANP [18].…”

Novel Biological Therapies Targeting Heart Failure

“…New natriuretic peptides and other vasodilators with additional biological properties are being developed to improve heart failure outcomes. Atrial natriuretic peptide (aka A-type NP, ANP) remains under investigation 64 . Cendiritide (CD- NP) is a recombinant engineered natriuretic peptide that combines elements of naturally occurring C- and D-type NP which optimizes its agonist action on both GC-A and B 65 , and may have unique anti-fibrotic activity.…”