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rdf:type | |
lifeskim:mentions | |
pubmed:dateCreated |
1994-4-4
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pubmed:abstractText |
Endothelin-1 (ET-1) is a powerful renal vasoconstrictor peptide that could be implicated in acute renal failure. The aim of this study was to test the effects of the endothelin-converting enzyme (ECE) inhibitor phosphoramidon on pressor responses to ET-1 and its precursor, big ET-1, in isolated perfused rat kidneys and in pithed rats. In Tyrode-perfused rat kidneys, both big ET-1 (0.2-0.4 nmol) and ET-1 (0.01-0.03 nmol) evoked dose-dependent constrictions. Phosphoramidon (10 microM) selectively inhibited the pressor responses to big ET-1 without altering those to ET-1, norepinephrine, angiotensin I (AT-I), or angiotensin II (AT-II). The metalloprotease inhibitor thiorphan, but not the angiotensin-converting enzyme (ACE) inhibitor perindoprilate, also selectively inhibited the renal constrictions caused by big ET-1 but not those induced by ET-1. In vivo, both big ET-1 and ET-1 (0.5-2 nmol/kg) evoked pressor responses that were augmented by indomethacin (15 mg/kg) and L-NNA (1 mg/kg/min). Phosphoramidon selectively inhibited the pressor responses to big ET-1 (ID50: 78 micrograms/kg/min) without affecting those to ET-1, AT-I, or AT-II. These data illustrate that the pressor responses to big ET-1 in the rat, both in vivo and in vitro, are due to its conversion into ET-1 by a phosphoramidon-sensitive ECE. In the rat, phosphoramidon selectively inhibits ECE but not ACE both in vitro and in vivo.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Angiotensin I,
http://linkedlifedata.com/resource/pubmed/chemical/Angiotensin II,
http://linkedlifedata.com/resource/pubmed/chemical/Aspartic Acid Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Endothelin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Endothelins,
http://linkedlifedata.com/resource/pubmed/chemical/Glycopeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Metalloendopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Norepinephrine,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Precursors,
http://linkedlifedata.com/resource/pubmed/chemical/endothelin-converting enzyme,
http://linkedlifedata.com/resource/pubmed/chemical/phosphoramidon
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pubmed:status |
MEDLINE
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pubmed:issn |
0160-2446
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
22 Suppl 8
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
S81-4
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:7510006-Angiotensin I,
pubmed-meshheading:7510006-Angiotensin II,
pubmed-meshheading:7510006-Animals,
pubmed-meshheading:7510006-Aspartic Acid Endopeptidases,
pubmed-meshheading:7510006-Blood Pressure,
pubmed-meshheading:7510006-Decerebrate State,
pubmed-meshheading:7510006-Endothelin-1,
pubmed-meshheading:7510006-Endothelins,
pubmed-meshheading:7510006-Glycopeptides,
pubmed-meshheading:7510006-Hemodynamics,
pubmed-meshheading:7510006-Kidney,
pubmed-meshheading:7510006-Male,
pubmed-meshheading:7510006-Metalloendopeptidases,
pubmed-meshheading:7510006-Norepinephrine,
pubmed-meshheading:7510006-Protein Precursors,
pubmed-meshheading:7510006-Rats,
pubmed-meshheading:7510006-Rats, Sprague-Dawley,
pubmed-meshheading:7510006-Rats, Wistar
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pubmed:year |
1993
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pubmed:articleTitle |
Phosphoramidon inhibits the conversion of big ET-1 into ET-1 in the pithed rat and in isolated perfused rat kidneys.
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pubmed:affiliation |
Servier Research Institute, Division of Angiology, Suresnes, France.
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pubmed:publicationType |
Journal Article,
In Vitro
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