Possible involvement of angiotensin I-converting enzyme in the inactivation of bradykinin by intact macrophages.

As intact macrophages inactivated bradykinin, the subcellular localization of the bradykinin-inactivating activity was studied using guinea-pig macrophages. The bradykinin-inactivating activity was found to be present in membrane and cytosol fractions but not in granular and nuclear fractions. The bradykinin-inactivating activity of the membrane fraction was inhibited by captopril, a specific inhibitor of angiotensin I-converting enzyme, whereas that of the cytosol fraction was hardly inhibited by various proteinase inhibitors used. Angiotensin I-converting enzyme activity was located predominantly in the membrane fraction and its activity was inhibited by captopril. Angiotensin I-converting enzyme activity measured with a synthetic substrate was competitively inhibited by bradykinin, suggesting that bradykinin is a possible substrate for macrophage angiotensin I-converting enzyme. When macrophages were modified chemically by diazotized sulfanilic acid, a poorly permeant reagent, both the bradykinin-inactivating activity and the angiotensin I-converting enzyme activity of macrophages decreased significantly without any inhibition of the cytosol bradykinin-inactivating activity. These findings seem to suggest that the angiotensin I-converting enzyme would be responsible for the inactivation of bradykinin in intact macrophages.