Elsevier

Life Sciences

Volume 63, Issue 4, 19 June 1998, Pages PL65-PL70
Life Sciences

Pharmacology letter Accelerated communication
Antihypertensive effect of a proteasome inhibitor in DOCA-salt hypertensive rats

https://doi.org/10.1016/S0024-3205(98)00276-8Get rights and content

Abstract

To search for a possible role for vascular proteasome in hypertension, we examined changes in proteasome level in aorta of deoxycorticosterone acetate (DOCA)-salt hypertensive rats and evaluated the antihypertensive effect of a proteasome inhibitor, N-benzyloxycarbonyl-Ile-Glu-(O-t-Bu)-Ala-leucinal (PSI). Two weeks after the start of DOCA-salt treatment, the rats, with systolic blood pressure being 154 ± 5 mmHg, were randomly divided into two groups and were given PSI or its vehicle for 2 weeks. Vehicle-treated DOCA-salt rats developed marked hypertension after 4 weeks (198 ± 9 mmHg), with increases in aortic proteasome activity and content. The systolic blood pressure was positively correlated with both the content and activity of aortic proteasome. The administration of PSI to DOCA-salt hypertensive rats suppressed the elevation of systolic blood pressure (144 ± 4 mmmHg), accompanied by decreases in aortic proteasome activity and content. These results suggest that proteasome production in vascular tissues is increased in DOCA-salt hypertensive rats, and that PSI exhibits antihypertensive effect in this experimental hypertensive model. Thus, the findings indicate the pathophysiological importance of increased vascular proteasome in the development of DOCA-salt hypertension.

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