Shinji Teramoto1,*, Masashi Suzuki2, Takeshi Matsuse3,
Takeo Ishii2, Yoshinosuke Fukuchi4 and Yasuyoshi Ouchi2
1Departmentﾊof Internal Medicine, San-no Hospital, (Clinical
Research Center, International University of Health and Welfare),
Tokyo 107-0052, Japan
2Departmentﾊof Geriatric Medicine, Tokyo University Hospital,
Tokyo 113-8655, Japan
3Departmentﾊof Pulmonary Medicine, Yokohama City University Medical
Center, Yokohama 232-0024, Japan
4Departmentﾊof Respiratory Medicine, Juntendo University School
of Medicine, Tokyo 113-8421, Japan
*ﾊAddress for correspondence: San-no Hospital, 8-5-35 Akasaka, Minato-ku,
Tokyo 107-0052, Japan
Abstract: We examined the effects of angiotensin-converting enzyme
(ACE) inhibitors on spontaneous or stimulated generation of reactive oxygen
species (ROS) by bronchoalveolar lavage (BAL) cells prepared from 6 patients
with chronic obstructive pulmonary disease (COPD) and from age-matched control
subjects without COPD. The ROS produced by BAL cells were measured by the
lucigenin-dependent chemiluminescence method. The application of ACE inhibitors
into culture media containing BAL cells inhibited spontaneous and stimulated
generation of ROS by BAL cells from COPD patients and control subjects in
an ambroxol-concentration-dependent manner. Alacepril, an ACE inhibitor
bearing SH-group, inhibited the oxygen radical production and generation
by BAL cells from COPD patients in a dose-dependent fashion. Approximately
0.6-0.7ﾊmM of alacepril inhibited 50% of the ROS production by BAL cells
from COPD patients, whereas a slightly higher concentration (3ﾊmM) of lisinopril,
an ACE inhibitor not bearing an SH-group, was necessary to inhibit the production
of ROS. These results suggest that an ACE inhibitor may act as an pulmonary
antioxidant in patients with COPD.
Keywords: Angiotensin-converting enzyme inhibitor, Oxygen radical, Chemiluminescence,
Bronchoalveolar lavage, Chronic obstructive pulmonary disease