Abstract
Deoxycorticosterone acetate (DOCA)-salt-treated rats developed marked hypertension after 4 weeks with an increase in aortic endothelin-1. Treatment of DOCA-salt hypertensive rats with a proteasome inhibitor, N-benzyloxycarbonyl-Ile-Glu(O-t-Bu)-Ala-leucinal, significantly reduced the elevation in systolic blood pressure and the effect was accompanied by a decrease in aortic endothelin- content. Thus, a proteasome-dependent proteolytic pathway appears to play an important role in the enhanced production of endothelin-1 in blood vessels and the consequent increase in blood pressure in this model of hypertension.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Aorta / metabolism
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Blood Pressure / drug effects
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Cysteine Endopeptidases / drug effects
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Cysteine Endopeptidases / metabolism*
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Desoxycorticosterone
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Endothelin-1 / biosynthesis
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Endothelin-1 / metabolism*
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Enzyme Inhibitors / pharmacology
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Hypertension / chemically induced
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Hypertension / metabolism*
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Male
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Multienzyme Complexes / drug effects
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Multienzyme Complexes / metabolism*
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Oligopeptides / pharmacology
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Proteasome Endopeptidase Complex
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Rats
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Rats, Sprague-Dawley
Substances
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Endothelin-1
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Enzyme Inhibitors
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Multienzyme Complexes
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Oligopeptides
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benzyloxycarbonyl-isoleucyl-glutamyl(O-tert-butyl)-alanyl-leucinal
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Desoxycorticosterone
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Cysteine Endopeptidases
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Proteasome Endopeptidase Complex