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 ac etate (PMA) stimulation of lung alveolar macrophages. Lung free cells, pred ominantly pulmonary alveolar macrophages, were obtained from Fischer 344 ra ts and guinea pigs using bronchoalveolar lavage. The oxygen radicals produc ed by pulmonary alveolar macrophages with or without stimulation of PMA wer e measured by lucigenin-dependent chemiluminescence method using a photon c ounter, Lumat 9501 (Berthold, Germany). Alacepril, an ACE inhibitor with SH -group, inhibited the oxygen radical production and generation by lung alve olar macrophages harvested from both rats and guinea pigs in a dose-depende nt fashion. Approximately 0.3 mM of alacepril inhibited 50% of oxygen radic al production of lung alveolar macrophages in both rats and guinea pigs, wh ereas a higher concentration (1-5 mM) of lisinopril, an ACE inhibitor witho ut SH-group, was necessary ta inhibit 50% of oxygen radical production of l ung alveolar macrophages in the animals. These results suggest that an ACE inhibitor with SH-group acts as an antioxidant in murine lungs and the trea tment with the ACE inhibitor may reduce oxidant stress in hypertensive pati ents with asthma.