Inhibition of neutral endopeptidase 3.4.24.11 in conscious dogs with pacing induced heart failure

Aa, Seymour; Mm, Asaad; Vm, Lanoce; Sa, Fennell; Hs, Cheung; Rogers, W.L.

doi:10.1093/cvr/27.6.1015

Cited by 25 publications

(11 citation statements)

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“…These inhibitory effects of UK73967 in vivo treatment on neutrophilrelated activities (adherence to coronary vascular endothelium, accumulation in the vasculature and myocardial tissue) were at least partially mediated by the inhibition of neutrophil NEP since the present in vivo dog experiment also showed that NEP was expressed in dog neutrophils and up-regulated in the circulated peripheral dog neutrophils after the myocardial ischemia/reperfusion and in the isolated dog neutrophils after C5a activation. The present and other studies with in vivo human and animals show that levels of ANP in the peripheral circulation were increased after systemic administration of NEP inhibitor (61,62). Thus, NEP inhibitor might inhibit neutrophils-mediated endothelial and myocardial injury and improve cardiac hemodynamics through the effect of ANP and BNP increased locally on the surface of neutrophils and systematically in the peripheral circulation by inhibition of NEP in neutrophils and in other organs.…”

Section: Discussionsupporting

confidence: 65%

Neutral endopeptidase 24.11 in neutrophils modulates protective effects of natriuretic peptides against neutrophils-induced endothelial cytotoxity.

Matsumura

Kugiyama²,

Sugiyama³

et al. 1996

J. Clin. Invest.

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Section: Discussionsupporting

confidence: 65%

Neutral endopeptidase 24.11 in neutrophils modulates protective effects of natriuretic peptides against neutrophils-induced endothelial cytotoxity.

Matsumura

Kugiyama²,

Sugiyama³

et al. 1996

J. Clin. Invest.

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“…20,21 This results in increased degradation of filtered ANF, as demonstrated by the fact that administration of neutral endopeptidase inhibitors increases the renal actions of ANF in volume-expanded states, including the DOCA-salt model. [21][22][23][24][25] The significant decrease of renal ANF mRNA in DOCA-salt hypertension found in the present investigation suggests that this decrease, together with increased degradation of blood-borne ANF, could play a pathogenic role in the development of mineralocorticoid hypertension. Supporting this view is our previous finding that blockade of the natriuretic peptide receptor impairs the ability of the kidneys to escape the salt-retaining effects of mineralocorticoid administration.…”

Section: Discussionsupporting

confidence: 47%

Variable Renal Atrial Natriuretic Factor Gene Expression in Hypertension

et al. 1999

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Abstract-We have previously established the existence of atrial natriuretic factor (ANF) gene expression within the renal parenchyma. Neither the role nor the regulation of this extracardiac source of ANF is clearly defined. To determine whether renal ANF gene expression, similar to cardiac expression, is linked to the activity of the renin-angiotensin system (RAS), we compared renal ANF gene expression in rats after suprarenal aortic banding, a hypertension model associated with activation of RAS, and in the deoxycorticosterone acetate (DOCA)-salt model, which is characterized by depression of RAS. Renal ANF mRNA was measured with a quantitative competitive reverse transcription polymerase chain reaction method. DOCA-salt hypertension significantly reduced the expression of renal ANF. In contrast, aortic banding significantly increased renal ANF expression. In both cases, ANF gene expression in the heart increased. Ramipril treatment at 10 g/kg of aortic-banded rats, a treatment that specifically affects local RAS but maintains hypertension, normalized renal ANF mRNA levels. Altogether, these results suggest that renal ANF gene expression is modulated by local RAS and is independent of circulating RAS and hypertension per se. The marked decrease of renal ANF mRNA in DOCA-salt hypertension suggests a pathogenic role for renal ANF gene downregulation by decreasing the sodium excretory mechanism mediated by the local expression of ANF acting on receptors found in the inner medullary collecting ducts. In aortic banding, renal ANF gene expression upregulation suggests a local compensatory function consistent with the consensus role of natriuretic peptides in the modulation of RAS, thus ameliorating the sodium-retaining effects of renal underperfusion. (Hypertension. 1999;33:1342-1347.)Key Words: atrial natriuretic factor Ⅲ renin-angiotensin system Ⅲ kidney Ⅲ deoxycorticosterone Ⅲ hypertension, renal T he polypeptide hormone atrial natriuretic factor (ANF) plays a significant role in modulating blood volume and blood pressure through cGMP-mediated actions on several target organs. 1 ANF is mainly of atrial origin, but it is also synthesized in other tissues, including the renal parenchyma. 2 Recently, we succeeded in reliably measuring ANF mRNA levels in kidney using a quantitative competitive reverse transcription polymerase chain reaction (QC-RT-PCR) and found that 1 week of deoxycorticosterone acetate (DOCA)-salt administration to rats, a treatment known to increase atrial ANF gene expression without modifying blood pressure, 3 resulted in a significant decrease in renal ANF gene expression. 2 Neither the role nor the regulation of this extracardiac source of ANF is known.Because the renin-angiotensin system (RAS) and ANF often play counterregulatory roles, we took advantage of the known inhibiting effect of the DOCA-salt treatment on RAS on the one hand and the upregulation of RAS after aortic banding on the other to substantiate the hypothesis that renal ANF gene expression may be influenced by RAS status. Furth...

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“…Inhibition of NEP potentiates the vasodilator, diuretic, and natriuretic effects of these two peptidergic systems and has beneficial effects in animal models of heart failure (Seymour et al 1993;Rademaker et al 1996;Willenbrock et al 1996). It may thus be postulated that the simultaneous inhibition of ACE and NEP may be superior to ACE inhibition alone post-MI.…”

Section: Introductionmentioning

confidence: 99%

Effects of captopril and omapatrilat on early post-myocardial infarction survival and cardiac hemodynamics in rats: interaction with cardiac cytokine expression

Blais¹,

Lapointe²,

Rouleau³

et al. 2002

Can. J. Physiol. Pharmacol.

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The purpose of this study was to evaluate and compare the effects of simultaneous angiotensin-converting enzyme (ACE) and neutral endopeptidase 24.11 (NEP) inhibition by the vasopeptidase inhibitor omapatrilat (10 and 40 mg x kg(-1) x day(-1)) with those of the selective ACE inhibitor captopril (160 mg x kg(-1) x day(-1)) on survival, cardiac hemodynamics, and cytokine mRNA expression in left ventricular (LV) tissues 4 days after myocardial infarction (MI) in rats. The effects of the co-administration of both B1 and B2 kinin receptor antagonists (2.5 mg x kg(-1) x day(-1) each) with and without omapatrilat were also evaluated to assess the role of bradykinin (BK) during this post-MI period. Both omapatrilat and captopril treatments improve early (4 days) post-MI survival when started 4 h post-MI. The use of kinin receptor antagonists had no significant effect on survival in untreated MI rats and omapatrilat-treated MI rats. This improvement in survival with omapatrilat and captopril is accompanied by a reduced LV end-diastolic pressure (LVEDP) and pulmonary congestion. The use of kinin receptor antagonists had little effect on cardiac hemodynamics or morphologic measurements. Acute MI significantly increased the expression of cardiac cytokines (TNF-alpha, TGF-beta1, and IL-10). Captopril significantly attenuated this activation, while omapatrilat had variable effects: sometimes increasing but generally not changing activation depending on the cytokine measured and the dose of omapatrilat used. The co-administration of both kinin receptor antagonists attenuates the increase in expression of cardiac TNF-alpha and TGF-beta1 after omapatrilat treatment. Taken together, these results would suggest that despite very marked differences in the way these drugs modified the expression of cardiac cytokines, both omapatrilat and captopril improved early (4 days) post-MI survival and cardiac function to a similar extent.

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Inhibition of neutral endopeptidase 3.4.24.11 in conscious dogs with pacing induced heart failure

Abstract: Inhibition of neutral endopeptidase in dogs with pacing induced heart failure protected endogenous atrial natriuretic peptide from degradation and stimulated sustained natriuresis, presumably via a tubular mechanism.

Cited by 25 publications

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Neutral endopeptidase 24.11 in neutrophils modulates protective effects of natriuretic peptides against neutrophils-induced endothelial cytotoxity.

Neutral endopeptidase 24.11 in neutrophils modulates protective effects of natriuretic peptides against neutrophils-induced endothelial cytotoxity.

Variable Renal Atrial Natriuretic Factor Gene Expression in Hypertension

Effects of captopril and omapatrilat on early post-myocardial infarction survival and cardiac hemodynamics in rats: interaction with cardiac cytokine expression

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