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. Tr eatment 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 accompanie d by a decrease in aortic endothelin-1 content. Thus, a proteasome-dep endent proteolytic pathway appears to play an important role in the en hanced production of endothelin-1 in blood vessels and the consequent increase in blood pressure in this model of hypertension. (C) 1998 Els evier Science B.V. All rights reserved.