Effects of angiotensin-converting enzyme (ACE) inhibitors on oxygen radical production and generation by murine lung alveolar macrophages.
We examined the effect of angiotensin-converting enzyme (ACE) inhibitors on oxygen radical production before and generation after phorbol-myristate acetate (PMA) stimulation of lung alveolar macrophages. Lung free cells, predominantly pulmonary alveolar macrophages, were obtained from Fischer 344 rats and guinea pigs using bronchoalveolar lavage. The oxygen radicals produced by pulmonary alveolar macrophages with or without stimulation of PMA were measured by lucigenin-dependent chemiluminescence method using a photon counter, Lumat 9501 (Berthold, Germany). Alacepril, an ACE inhibitor with SH-group, inhibited the oxygen radical production and generation by lung alveolar macrophages harvested from both rats and guinea pigs in a dose-dependent fashion. Approximately 0.3 mM of alacepril inhibited 50% of oxygen radical production of lung alveolar macrophages in both rats and guinea pigs, whereas a higher concentration (1-5 mM) of lisinopril, an ACE inhibitor without SH-group, was necessary to inhibit 50% of oxygen radical production of lung alveolar macrophages in the animals. These results suggest that an ACE inhibitor with SH-group acts as an antioxidant in murine lungs and the treatment with the ACE inhibitor may reduce oxidant stress in hypertensive patients with asthma.
Suzuki
M
M
Department of Geriatric Medicine, Tokyo University Hospital, Japan.
Teramoto
S
S
Katayama
H
H
Ohga
E
E
Matsuse
T
T
Ouchi
Y
Y
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002216:Captopril / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D017706:Lisinopril / Q000494:pharmacology; D008163:Luminescent Measurements; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D017382:Reactive Oxygen Species; D002216:Captopril; D017706:Lisinopril; D013755:Tetradecanoylphorbol Acetate; C046835:alacepril