Jpn. J. Pharmacol. 83 (1), 56-62 (2000)

Effects of Angiotensin-Converting Enzyme Inhibitors on Spontaneous or Stimulated Generation of Reactive Oxygen Species by Bronchoalveolar Lavage Cells Harvested From Patients With or Without Chronic Obstructive Pulmonary Disease

Shinji Teramoto1,*, Masashi Suzuki2, Takeshi Matsuse3, Takeo Ishii2, Yoshinosuke Fukuchi4 and Yasuyoshi Ouchi2

1Department╩of Internal Medicine, San-no Hospital, (Clinical Research Center, International University of Health and Welfare),
Tokyo 107-0052, Japan
2Department╩of Geriatric Medicine, Tokyo University Hospital, Tokyo 113-8655, Japan
3Department╩of Pulmonary Medicine, Yokohama City University Medical Center, Yokohama 232-0024, Japan
4Department╩of Respiratory Medicine, Juntendo University School of Medicine, Tokyo 113-8421, Japan
*╩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╩mM of alacepril inhibited 50% of the ROS production by BAL cells from COPD patients, whereas a slightly higher concentration (3╩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

Copyrightę The Japanese Pharmacological Society 2000

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