Inhibitors of ANF metabolism. Potential therapeutic agents in cardiovascular disease.

Effects of Renal Neutral Endopeptidase Inhibition on Sodium Excretion, Renal Hemodynamics and Neuro-hormonal Activation in Patients with Congestive Heart Failure

“…Previous work has documented that most cGMP found in the urine is synthesized in the kidney [17], and that cGMP production specifically reflects ANF activity [ 1,18], Consequently, candoxatril appears to have a pref erential renal effect leading to natriuresis, an effect pre viously postulated with other neutral endopeptidase in hibitors, to be mediated at the level of the renal tubules [7,19]. Although some authors have questioned the ability of augmented tubular ANF concentration to promote natriuresis [20], our findings are consistent with those of others who have postulated that neutral endopeptidase inhibi tion confers a protective effect to filtered ANF. allowing enhanced distal delivery of the peptide to medullary col lecting ducts where the natriuretic action of the peptide is effected [ 19].…”

Regulation of Extracellular Fluid Volume by Integrated Control of Sodium Excretion

“…ANP is a 28-amino acid peptide hormone that is synthesized by atrial myocytes and secreted in response to increased atrial distention. Conversely, ANP secretion is reduced in response to reductions in atrial pressure (1,3,5). The quantitative importance of ANP in controlling sodium excretion is uncertain due to the lack of effort via experimental tools to block the synthesis or effector site of ANP.…”

Neutral endopeptidase (EC 3.4.24.11) in cirrhotic liver: A new target to treat portal hypertension?

“…NEP has been found in the brush border membrane of kidney tubule cells, in bronchial fibroblasts and epithelial cells, in B lymphoid-progenitors, and in glial cells [13]. NEP degrades opioid-peptides [14], bradykinin [15], bombesin-like peptide [16], substance P [17], endogenous natriuretic peptides [18,19], and adrenomedullin [20], as well as endothelin-1 (ET-1) [21] and angiotensin II [17]. NEP can produce the vasoconstrictor polypeptide ET-1 from circulating precursors (i.e.…”