Modulation of proteolytic activity in tissues following chronic inhibition of angiotensin-converting enzyme.

The release of angiotensin-converting enzyme (ACE) (EC 3.4.15.1) from aortic rings and the modulation of the proteolytic balance of rat organs under chronic ACE inhibition were examined. ACE from rat organs had a higher apparent molecular mass than the circulating enzyme, but a similar behavior towards ACE inhibitors. Chronic treatment with ACE inhibitors (captopril or lisinopril) for 25 days, followed by 1 day without treatment, increased plasma ACE, but only slightly modified lung, aorta, heart and kidney specific ACE activity. In the lung the activities of aminopeptidases A and B, two angiotensin degrading enzymes, decreased, as did the activity of aminopeptidase A in the plasma. In vitro, the release of ACE from aortic rings was not suppressed by inhibitors of either serine proteases, metalloproteases, serine and thiol proteases, or aspartyl proteases. After chronic ACE inhibition, the release of ACE from aortic rings was not significantly modified by the presence of protease inhibitors. As shown by gel filtration experiments, ACE was converted from its tissue form into its circulating form only after release from the endothelium.