Omapatrilat or lisinopril in salt-sensitive hypertensives

Campese, Vito M.; Ferrario, Carlos M.; Ruddy, Michael C.; Grim, C E; Smith, Ronald D.; Lasseter, Kenneth C.; Smith, William B.; Vargas, Ruperto; Habashy, M.; Delaney, Carol; Ge, Zhenzhong; Liao, Weitang

doi:10.1016/s0895-7061(00)00338-1

Cited by 4 publications

(2 citation statements)

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“…The short half-life of ANP [20], together with the physiologic regulation [21,22] of circulating concentrations of ANP, may have counteracted any tendency toward increased plasma ANP concentrations consequent to the inhibition of ANP degradation by omapatrilat in young healthy volunteers. Omapatrilat significantly increased plasma concentrations of ANP in patients with salt-sensitive hypertension [23] and in patients with heart failure [24].…”

Section: Omapatrilat-induced Inhibition Of Nep In Humansmentioning

confidence: 94%

Effects of omapatrilat on pharmacodynamic biomarkers of neutral endopeptidase and angiotensin-converting enzyme activity in humans

Vesterqvist

Reeves

2001

Current Science Inc

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Vasopeptidase inhibition is a new concept in blood pressure management. A single molecule simultaneously inhibits two enzymes that regulate cardiovascular function: neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE)[1]. Development of vasopeptidase inhibitors stemmed from the need for new and more efficacious antihypertensive agents that not only reduce blood pressure but also treat hypertension as part of a larger syndrome involving endothelial dysfunction [2]. By inhibiting NEP and ACE, vasopeptidase inhibitors enhance the natriuretic peptide and kallikrein-kinin systems and inhibit the renin-angiotensin-aldosterone system. This article outlines the pharmacodynamic effects of the vasopeptidase inhibitor omapatrilat on biomarkers of NEP and ACE activity in humans.

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Section: Omapatrilat-induced Inhibition Of Nep In Humansmentioning

confidence: 94%

Effects of omapatrilat on pharmacodynamic biomarkers of neutral endopeptidase and angiotensin-converting enzyme activity in humans

Vesterqvist

Reeves

2001

Current Science Inc

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“…In 57 patients with salt-sensitive hypertension, 40 mg/d omapatrilat revealed a greater reduction in systolic, diastolic, and mean arterial pressure compared with 20 mg/d lisinopril [37]. Omapatrilat exhibited long-lasting antihypertensive effects in 83 patients even 2 weeks after withdrawal of longterm (2 months) treatment [38], and was even more effective when combined with diuretics [39].…”

Section: Vasopeptidase Inhibitors In the Treatment Of Hypertensionmentioning

confidence: 99%

Vasopeptidase inhibition: Effective blood pressure control for vascular protection

Quaschning

Ruschitzka²,

Lüscher³

2002

Current Science Inc

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Angiotensin converting enzyme (ACE) inhibition is a well-established principle in the treatment of hypertension, and numerous large scale clinical studies have clearly demonstrated the beneficial effects of inhibiting the renin-angiotensin-aldosterone system (RAS) in hypertension. The clinical success of ACE inhibitors encouraged attempts to inhibit other key enzymes in the regulation of vascular tone, such as the neutral endopeptidase (NEP). Similar to ACE, NEP is an endothelial cell surface metalloproteinase, which is involved in the degradation of several regulatory peptides including the natriuretic peptides, and augments vasodilatation and natriuresis through increased levels of atrial natriuretic peptide. By inhibiting the RAS and potentiating the natriuretic peptide system at the same time, combined NEP/ACE inhibitors, the so-called "vasopeptidase inhibitors," reduce vasoconstriction and enhance vasodilatation, and in turn decrease peripheral vascular resistance and blood pressure. Within the vessel wall this may lead to a reduction of vasoconstrictor and proliferative mediators such as angiotensin II and endothelin-1, and may increase local levels of bradykinin as well as natriuretic peptides. Based on these considerations, numerous preclinical studies with vasopeptidase inhibitors have been performed and reveal promising results in experimental hypertension. Correspondingly, large-scale clinical studies in patients with hypertension are on the way, to transfer the principle of vasopeptidase inhibition from bench to bedside.

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Hypertension

2006

Wiley Handbook of Current and Emerging Drug Therapies

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Omapatrilat or lisinopril in salt-sensitive hypertensives

Cited by 4 publications

References 0 publications

Effects of omapatrilat on pharmacodynamic biomarkers of neutral endopeptidase and angiotensin-converting enzyme activity in humans

Effects of omapatrilat on pharmacodynamic biomarkers of neutral endopeptidase and angiotensin-converting enzyme activity in humans

Vasopeptidase inhibition: Effective blood pressure control for vascular protection

Hypertension

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