A proteasome inhibitor lessens the increased aortic endothelin-1 content in deoxycorticosterone acetate-salt hypertensive rats.
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.
Okamoto
H
H
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan.
Takaoka
M
M
Ohkita
M
M
Itoh
M
M
Nishioka
M
M
Matsumura
Y
Y
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D003546:Cysteine Endopeptidases / Q000187:drug effects / Q000378:metabolism*; D003900:Desoxycorticosterone; D019332:Endothelin-1 / Q000096:biosynthesis / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D009097:Multienzyme Complexes / Q000187:drug effects / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex; D051381:Rats; D017207:Rats, Sprague-Dawley
D019332:Endothelin-1; D004791:Enzyme Inhibitors; D009097:Multienzyme Complexes; D009842:Oligopeptides; C090535:benzyloxycarbonyl-isoleucyl-glutamyl(O-tert-butyl)-alanyl-leucinal; D003900:Desoxycorticosterone; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex