A proteasome inhibitor prevents vascular hypertrophy in deoxycorticosterone acetate-salt hypertensive rats

1. In the present study, we investigated the potential of the proteasome in hibitor N-benzyloxycarbonyl-Ile-Glu(O-t-Bu)-Ala-leucinal (PSI) to prevent v ascular hypertrophy induced by deoxycorticosterone acetate (DOCA) and salt in rats. 2. Vehicle (35% ethanol, 35% polyethylene glycol and 30% saline solution)-t reated DOCA-salt rats developed marked hypertension at 4 weeks. Morphologic al studies on the rats given vehicle showed aortic hypertrophy, with a sign ificant increase in wall thickness, wall area and wall-to-lumen ratio. A si gnificant decrease in vascular wall hypertrophy was observed in PSI (3 mg/k g)-treated DOCA-salt rats. In addition, a marked increase in aortic endothe lin (ET)-1 content was evident in vehicle-treated DOCA-salt rats compared w ith findings in sham-operated rats. A significant attenuation of this incre ase occurred in PSI-treated DOCA-salt rats. 3. These results indicate that PSI can prevent the vascular hypertrophy in DOCA-salt hypertensive rats and the effect is accompanied by suppression of ET-1 production in the aorta. We suggest that a proteasome-dependent prote olytic system has an important role in the development of vascular hypertro phy in cases of DOCA-salt-induced hypertension, possibly through the enhanc ement of ET-1 production in vascular tissues.