Inhibitory effects of angiotensin-converting enzyme (ACE) inhibitors on oxygen radicals produced by bronchoalveolar lavage cells in young and aged guinea pigs.

Abstract

We examined the effect of angiotensin-converting enzyme (ACE) inhibitors and age on oxygen radical formation by bronchoalveolar lavage (BAL) cells. Lung-free cells, including pulmonary alveolar macrophages, were harvested from young (4-month-old) and aged (28-month-old) male guinea pigs using BAL. The oxygen radicals produced by BAL cells were measured by a lucigenin-dependent chemiluminescence method using a photon counter. Although spontaneous oxygen radical production by BAL cells from young and aged guinea pigs did not differ, the oxygen radical generation after maximal stimulation with phorbol-myristate acetate (PMA) was greater than that produced without PMA stimulation in both young and aged animals. ACE inhibitors with and without an SH-group (alacepril and lisinopril, respectively) were tested for their effect on oxygen radical formation by BAL cells; both ACE inhibitors inhibited oxygen radical production and generation by BAL cells from both young and aged guinea pigs in a dose-dependent manner. However, the alacepril concentration giving 50% inhibition (IC50) of oxygen radical generation by BAL cells was smaller than the IC50 of lisinopril in both young and aged guinea pigs. These results indicate that ACE inhibitors, in particular those with an SH-group, effectively reduce oxygen radical production by BAL cells from young and aged guinea pigs, and suggest that treatment with ACE inhibitors may be useful for ameliorating oxidant-associated pulmonary disorders in young and aged patients.