Neutral endopeptidase inhibition potentiates the natriuretic actions of adrenomedullin

Lisý, Ondřej; Jougaski, M; Schirger, JA; Hh, Chen; Barclay, PT; Burnett, J. C.

doi:10.1016/s1071-9164(98)90067-7

Cited by 26 publications

(48 citation statements)

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“…Furthermore, following incubation for 4 h, the degradation of 125 I-labeled DNP remained attenuated by phenanthroline. The present findings are consistent with previous studies (17,18) and indicate the significance of NEP in the inactivation of DNP, similar to ANP, revealing that NEP is involved in the inactivation of BNP and ANP in the plasma. However, these observations are fairly different from an earlier study, which revealed that DNP was resistant to degradation by NEP (29).…”

Section: Discussionsupporting

confidence: 94%

“…The metabolic fate of ANP in plasma is well known (17), along with the fact that it is degraded by a neutral endopeptidase (NEP), which is a metallopeptidase (18). It has been reported that the rank order of hydrolysis by NEP in NPs is CNP>ANP>BNP, indicating that a longer length of the C-terminus of the peptide results in a greater resistance to hydrolysis by NEP (19).…”

Section: Discussionmentioning

confidence: 99%

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Dendroaspis natriuretic peptide is degraded by a metalloproteinase in the rat kidney

Kim

et al. 2013

Molecular Medicine Reports

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Abstract. Our previous study demonstrated that the concentration of dendroaspis natriuretic peptide (DNP) was markedly higher than that of atrial NP (ANP) in rabbit plasma, indicating that DNP has a different metabolic rate from other NPs. Therefore, the metabolic characteristics of DNP in mammals require further analysis. The stabilities of NPs were determined by incubating 125 I-labeled ANP, brain NP (BNP), C-type NP (CNP) and DNP at 37˚C for 1, 2 and 4 h, and analyzing their profiles by reversed-phase high-performance liquid chromatography.125 I-labeled ANP, BNP and CNP were quickly degraded in rat plasma, while 125 I-labeled DNP was stable for 4 h. The relative stability of the peptides following incubation in rat plasma followed the rank order of: DNP>>>ANP≥BNP>>CNP. Organs were also examined for the degradation of DNP, including the spleen, kidney, liver, heart and lung. The physiological target organ for the degradation of DNP was observed to be the kidney. Furthermore, degradation of DNP in the kidney was attenuated by phenanthroline, a metalloproteinase inhibitor. Therefore, these results indicate that DNP has a longer stability in plasma and that it may have strong therapeutic applications in cardiac disease.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Dendroaspis natriuretic peptide is degraded by a metalloproteinase in the rat kidney

Kim

et al. 2013

Molecular Medicine Reports

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“…A similar range of responses have previously been observed in animals 8 and humans with HF 10 after short-term AM administration, and are likely to be owing to the actions of AM to directly reduce tubular sodium reabsorption and renal vascular resistance and to increase renal blood flow. [21][22][23] A persistent increase in glomerular filtration rate, as assessed by the rise in creatinine clearance, also appears to have contributed to the sustained natriuretic effect observed in the current study. The maintenance of sodium excretion in association with the protracted reduction in MAP (and presumably renal perfusion pressure) points to a shift in the pressure-natriuresis curve with prolonged AM administration.…”

Section: Chronic Effects Of Adrenomedullin In Sheep With Experimentalmentioning

confidence: 50%

Long-Term Adrenomedullin Administration in Experimental Heart Failure

et al. 2002

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Abstract-Short-term administration of adrenomedullin, a recently discovered peptide with potent vasodilator, natriuretic, and aldosterone-inhibitory actions, has beneficial effects in experimental and clinical heart failure. The effects of prolonged adrenomedullin administration have not previously been assessed in this setting. Consequently, in 16 sheep with pacing-induced heart failure, we infused either adrenomedullin (10 ng/kg per minute; nϭ8) or a vehicle control (Hemaccel; nϭ8) for 4 days. Compared with control data, infusion of adrenomedullin persistently increased circulating levels of the peptide (by Ϸ9.5 pmol/L; PϽ0.001), in association with prompt (15 minutes) and sustained (4 days) increases in cardiac output (day 4, 27%), and reductions in peripheral resistance (30%), mean arterial pressure (13%), and left atrial pressure (24%; all, PϽ0.001). Adrenomedullin also significantly enhanced urinary sodium excretion (day 4, 3-fold; PϽ0.05), creatinine excretion (1.2-fold; PϽ0.001), and creatinine clearance (1.4-fold; PϽ0.001) over the 4 days of treatment, whereas urine volume and cAMP excretion tended to be elevated (both, 0.1ϾPϾ0.05). Plasma renin activity was increased (PϽ0.05), whereas aldosterone levels were reduced in a sustained fashion (PϽ0.01). Plasma endothelin rose transiently (hours 1 to 6) after initiation of treatment (PϽ0.05). Despite substantial cardiac unloading, plasma concentrations of the natriuretic peptides were not significantly different from control. In conclusion, long-term administration of adrenomedullin induces pronounced and sustained cardiovascular and renal effects in experimental heart failure, including reductions in cardiac preload and afterload, as well as augmentation of cardiac output, sodium excretion, and glomerular filtration. These findings support the concept of adrenomedullin as a protective hormone during hemodynamic compromise with therapeutic potential in heart failure.

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“…Two clearance pathways of tissue ADM have been recognized: protease hydrolysis and binding to ADM clearance receptors (2). Increased plasma ADM has been observed during systemic NEP inhibition, which confirms that ADM is a substrate of NEP (18). It was later confirmed that NEP is the major degradation enzyme of ADM and natriuretic peptides (8).…”

Section: Discussionmentioning

confidence: 92%

Relationship between the Contents of Adrenomedullin and Distributions of Neutral Endopeptidase in Blood and Tissues of Spontaneously Hypertensive Rats

et al. 2004

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Neutral endopeptidase inhibition potentiates the natriuretic actions of adrenomedullin

Cited by 26 publications

References 0 publications

Dendroaspis natriuretic peptide is degraded by a metalloproteinase in the rat kidney

Dendroaspis natriuretic peptide is degraded by a metalloproteinase in the rat kidney

Long-Term Adrenomedullin Administration in Experimental Heart Failure

Relationship between the Contents of Adrenomedullin and Distributions of Neutral Endopeptidase in Blood and Tissues of Spontaneously Hypertensive Rats

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