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A Proteasome Inhibitor Prevents Vascular Hypertrophy In Deoxycorticosterone Acetate‐Salt Hypertensive Rats
Author(s) -
Takaoka Masanori,
Ohkita Mamoru,
Itoh Makoto,
Kobayashi Yutaka,
Okamoto Hisako,
Matsumura Yasuo
Publication year - 2001
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2001.03461.x
Subject(s) - medicine , endocrinology , muscle hypertrophy , saline , aorta , lumen (anatomy) , chemistry
SUMMARY 1. In the present study, we investigated the potential of the proteasome inhibitor N ‐benzyloxycarbonyl‐Ile‐Glu( O ‐ t ‐Bu)‐Ala‐leucinal (PSI) to prevent vascular hypertrophy induced by deoxycorticosterone acetate (DOCA) and salt in rats. 2. Vehicle (35% ethanol, 35% polyethylene glycol and 30% saline solution)‐treated DOCA‐salt rats developed marked hypertension at 4 weeks. Morphological studies on the rats given vehicle showed aortic hypertrophy, with a significant increase in wall thickness, wall area and wall‐to‐lumen ratio. A significant decrease in vascular wall hypertrophy was observed in PSI (3 mg/kg)‐treated DOCA‐salt rats. In addition, a marked increase in aortic endothelin (ET)‐1 content was evident in vehicle‐treated DOCA‐salt rats compared with findings in sham‐operated rats. A significant attenuation of this increase 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 proteolytic system has an important role in the development of vascular hypertrophy in cases of DOCA‐salt‐induced hypertension, possibly through the enhancement of ET‐1 production in vascular tissues.