Enkephalinase inhibition increases plasma atrial natriuretic peptide levels, glomerular filtration rate, and urinary sodium excretion in rats with reduced renal mass

H. M. Lafferty, M. Gunning, P. Silva, M. B. Zimmerman, B. M. Brenner, Sharon Anderson

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

To investigate the in vivo effects of inhibition of endopeptidase 24.11, an enkephalinase enzyme shown to be involved in atrial natriuretic peptide (ANP) breakdown in vitro, we infused phosphoramidon, a specific inhibitor of endopeptidase 24.11, into rats with reduced renal mass (and chronic extracellular volume expansion) and into normal rats. Relative to baseline values in rats with remnant kidneys, phosphoramidon led to elevations of plasma ANP levels and concomitant increases in urinary sodium excretion, fractional excretion of sodium, glomerular filtration rate, filtration fraction, and urinary cyclic GMP excretion. Similar changes in renal function and urinary cyclic GMP excretion were obtained with thiorphan, another endopeptidase 24.11 inhibitor. These enhanced ANP levels and renal actions were not observed with phosphoramidon in normal rats. These results show that plasma ANP levels can be modulated in rats with reduced renal mass by inhibition of endopeptidase 24.11.

Original languageEnglish (US)
Pages (from-to)640-646
Number of pages7
JournalCirculation Research
Volume65
Issue number3
StatePublished - 1989
Externally publishedYes

Fingerprint

Neprilysin
Atrial Natriuretic Factor
Glomerular Filtration Rate
Sodium
Kidney
Cyclic GMP
Thiorphan
Protease Inhibitors
Enzymes
phosphoramidon

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Enkephalinase inhibition increases plasma atrial natriuretic peptide levels, glomerular filtration rate, and urinary sodium excretion in rats with reduced renal mass. / Lafferty, H. M.; Gunning, M.; Silva, P.; Zimmerman, M. B.; Brenner, B. M.; Anderson, Sharon.

In: Circulation Research, Vol. 65, No. 3, 1989, p. 640-646.

Research output: Contribution to journalArticle

@article{611919993bae4c589ec3db7652374559,
title = "Enkephalinase inhibition increases plasma atrial natriuretic peptide levels, glomerular filtration rate, and urinary sodium excretion in rats with reduced renal mass",
abstract = "To investigate the in vivo effects of inhibition of endopeptidase 24.11, an enkephalinase enzyme shown to be involved in atrial natriuretic peptide (ANP) breakdown in vitro, we infused phosphoramidon, a specific inhibitor of endopeptidase 24.11, into rats with reduced renal mass (and chronic extracellular volume expansion) and into normal rats. Relative to baseline values in rats with remnant kidneys, phosphoramidon led to elevations of plasma ANP levels and concomitant increases in urinary sodium excretion, fractional excretion of sodium, glomerular filtration rate, filtration fraction, and urinary cyclic GMP excretion. Similar changes in renal function and urinary cyclic GMP excretion were obtained with thiorphan, another endopeptidase 24.11 inhibitor. These enhanced ANP levels and renal actions were not observed with phosphoramidon in normal rats. These results show that plasma ANP levels can be modulated in rats with reduced renal mass by inhibition of endopeptidase 24.11.",
author = "Lafferty, {H. M.} and M. Gunning and P. Silva and Zimmerman, {M. B.} and Brenner, {B. M.} and Sharon Anderson",
year = "1989",
language = "English (US)",
volume = "65",
pages = "640--646",
journal = "Circulation Research",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

TY - JOUR

T1 - Enkephalinase inhibition increases plasma atrial natriuretic peptide levels, glomerular filtration rate, and urinary sodium excretion in rats with reduced renal mass

AU - Lafferty, H. M.

AU - Gunning, M.

AU - Silva, P.

AU - Zimmerman, M. B.

AU - Brenner, B. M.

AU - Anderson, Sharon

PY - 1989

Y1 - 1989

N2 - To investigate the in vivo effects of inhibition of endopeptidase 24.11, an enkephalinase enzyme shown to be involved in atrial natriuretic peptide (ANP) breakdown in vitro, we infused phosphoramidon, a specific inhibitor of endopeptidase 24.11, into rats with reduced renal mass (and chronic extracellular volume expansion) and into normal rats. Relative to baseline values in rats with remnant kidneys, phosphoramidon led to elevations of plasma ANP levels and concomitant increases in urinary sodium excretion, fractional excretion of sodium, glomerular filtration rate, filtration fraction, and urinary cyclic GMP excretion. Similar changes in renal function and urinary cyclic GMP excretion were obtained with thiorphan, another endopeptidase 24.11 inhibitor. These enhanced ANP levels and renal actions were not observed with phosphoramidon in normal rats. These results show that plasma ANP levels can be modulated in rats with reduced renal mass by inhibition of endopeptidase 24.11.

AB - To investigate the in vivo effects of inhibition of endopeptidase 24.11, an enkephalinase enzyme shown to be involved in atrial natriuretic peptide (ANP) breakdown in vitro, we infused phosphoramidon, a specific inhibitor of endopeptidase 24.11, into rats with reduced renal mass (and chronic extracellular volume expansion) and into normal rats. Relative to baseline values in rats with remnant kidneys, phosphoramidon led to elevations of plasma ANP levels and concomitant increases in urinary sodium excretion, fractional excretion of sodium, glomerular filtration rate, filtration fraction, and urinary cyclic GMP excretion. Similar changes in renal function and urinary cyclic GMP excretion were obtained with thiorphan, another endopeptidase 24.11 inhibitor. These enhanced ANP levels and renal actions were not observed with phosphoramidon in normal rats. These results show that plasma ANP levels can be modulated in rats with reduced renal mass by inhibition of endopeptidase 24.11.

UR - http://www.scopus.com/inward/record.url?scp=0024414555&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024414555&partnerID=8YFLogxK

M3 - Article

VL - 65

SP - 640

EP - 646

JO - Circulation Research

JF - Circulation Research

SN - 0009-7330

IS - 3

ER -