© 2000 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Dehydroepiandrosterone Retards Atherosclerosis Formation Through Its Conversion to Estrogen
The Possible Role of Nitric Oxide
From the Department of Geriatrics, Nagoya University School of Medicine, Nagoya, Japan.
Correspondence to Toshio Hayashi, Department of Geriatrics, Nagoya University School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550 Japan. E-mail hayashi{at}med.nagoya-u.ac.jp
Abstract—Dehydroepiandrosterone
(DHEA) is speculated to have an antiatherosclerotic effect,
although the mechanism of action remains unclear. The objective of
the current study was to determine whether the antiatherosclerotic
effect of DHEA is related to its conversion to estrogen and to define
the role of nitric oxide (NO) in the antiatherosclerotic effect of
DHEA. Forty-eight oophorectomized rabbits were divided into 5 groups
and fed the following diets for 10 weeks: group 1, a regular rabbit
diet plus 1% cholesterol (a high-cholesterol
diet [HCD]); group 2, an HCD plus 0.3% DHEA; group 3, an HCD plus
0.3% DHEA and fadrozole (2.0 mg · kg-1 ·
d-1), a specific aromatase inhibitor; group 4,
an HCD plus 17ß-estradiol (20 µg · kg-1
· d-1); and group 5, a regular diet. Atherosclerotic
lesions, lipid deposition in aortic vessels, and basal and stimulated
NO release were measured in the aforementioned groups of rabbits. NO
release was measured by using an NO-selective electrode as well as by
measuring vascular responses and the plasma NO metabolites nitrite and
nitrate. The plasma total cholesterol level was increased,
but there were no significant differences in lipid profile in the 4
groups of rabbits that were fed the HCD. The area occupied by
atherosclerosis in the thoracic aorta was diminished by
60% in the DHEA-treated rabbits (group 2) compared with the HCD
group of rabbits (group 1); there was a corresponding 80% decrease in
the estradiol group (group 4) but only a 30% decrease in the DHEA plus
fadrozole group (group 3). In the aortas of rabbits from groups 1 and
3, the acetylcholine-induced and tone-related basal NO-mediated
relaxations were diminished compared with those of the controls (group
5). However, these relaxations were restored in the aortas of group 2
and 4 rabbits, and an increase in NO release was observed in groups 2
and 4 compared with groups 1 and 3, as measured by an NO-selective
electrode. Injection of neither solvent (20% ethanol/distilled water)
nor fadrozole significantly affected the atherosclerotic area or the
NO-related responses described above. We conclude that 50% of the
total antiatherosclerotic effect of DHEA was achieved through the
conversion of DHEA to estrogen. NO may also play a role in the
antiatherosclerotic effect of DHEA and 17ß-estradiol.
Key Words: dehydroepiandrosterone • atherosclerosis • nitric oxide • estrogen • aromatase
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