Dual Endothelin-Converting Enzyme/Neutral Endopeptidase Inhibition

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Dual endothelin-converting enzyme/neutral endopeptidase inhibition: a novel treatment for renovascular hypertension beyond blood pressure lowering?

The endothelin (ET) family consists of three 21-amino acid peptides (ET-1, ET-2, and ET-3) with powerful vasoconstrictor and pressor properties.1 Of the 3 peptides, ET-1 is the major vascular isoform and of most importance in the cardiovascular system.2 The gene product is the 212amino acid preproET-1. This is cleaved to Big-ET-1, after which an ET-converting enzyme (ECE), of which there are se...

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Editorial Commentary Dual Endothelin-Converting Enzyme/Neutral Endopeptidase Inhibition A Novel Treatment for Renovascular Hypertension Beyond Blood Pressure Lowering?

The endothelin (ET) family consists of three 21-amino acid peptides (ET-1, ET-2, and ET-3) with powerful vasoconstrictor and pressor properties.1 Of the 3 peptides, ET-1 is the major vascular isoform and of most importance in the cardiovascular system.2 The gene product is the 212amino acid preproET-1. This is cleaved to Big-ET-1, after which an ET-converting enzyme (ECE), of which there are se...

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Dual endothelin-converting enzyme/neutral endopeptidase blockade in rats with D-galactosamine-induced liver failure

Secondary activation of the endothelin system is thought to be involved in toxic liver injury. This study tested the hypothesis that dual endothelin-converting enzyme / neutral endopeptidase blockade might be able to attenuate acute toxic liver injury. - Male Sprague-Dawley rats were implanted with subcutaneous minipumps to deliver the novel compound SLV338 (10 mg/kg*d) or vehicle. Four days la...

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Modulation of functionally active endothelin-converting enzyme by chronic neutral endopeptidase inhibition in experimental atherosclerosis.

BACKGROUND Endothelin-converting enzyme-1 (ECE-1) processes big endothelin-1 (ET-1) to ET-1, a peptide implicated in atheroma formation. ECE-1 exists in 2 isoforms (ECE-1alpha and ECE-1beta), the result of alternative splicing of a common gene. Neutral endopeptidase (NEP) is a genetically distinct metallopeptidase that degrades the natriuretic peptides. These peptides mediate antiproliferative ...

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The dual endothelin converting enzyme/neutral endopeptidase inhibitor SLV-306 (daglutril), inhibits systemic conversion of big endothelin-1 in humans.

AIMS Inhibition of neutral endopeptidases (NEP) results in a beneficial increase in plasma concentrations of natriuretic peptides such as ANP. However NEP inhibitors were ineffective anti-hypertensives, probably because NEP also degrades vasoconstrictor peptides, including endothelin-1 (ET-1). Dual NEP and endothelin converting enzyme (ECE) inhibition may be more useful. The aim of the study wa...

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ژورنال

عنوان ژورنال: Hypertension

سال: 2011

ISSN: 0194-911X,1524-4563

DOI: 10.1161/hypertensionaha.110.166876