Angiotensin-converting enzyme activity in postmortem human tissues.

Angiotensin-converting enzyme (ACE) was assayed spectrophotometrically with hippuryl-histidyl-leucine as substrate. Postmortem tissues from 11 patients with various causes of death and pancreatic juice obtained during endoscopic cannulation of the pancreatic duct were assayed. Activity of most human tissues other than those of the gastrointestinal tract were found to be predominantly associated with the particulate fraction of the homogenates. Tissues with more than twice the ACE activity of lung included kidney, ileum, duodenum, and uterus; seven tissues with ACE activity approximately equal to that of lung included prostate, jejunum, lymph node, thyroid, colon, testis, and adrenal. Twelve other tissues had lower levels of activity with the heart consistently showing the least ACE activity. In the small intestine, the level of ACE activity increased with increasing distance from the pylorus. Inhibitors of ACE were detected in most tissues by assaying serial dilutions of the tissue homogenate; the presence of partial inhibitors did not significantly affect the relative activities of the various tissues. Lysis of hippuryl-histidyl-leucine by the pancreas and pancreatic juice resulted from an enzyme believed to be carboxypeptidase A which is present as a zymogen and activated by trypsin; this activity differed from ACE in that it had a smaller molecular weight (25,000) compared with ACE of serum (240,000), and it was not strongly inhibited by ethylenediaminetetraacetic acid or SQ 20881 (a specific ACE inhibitor). These studies show that human tissues vary in their content of ACE and suggest that ACE may serve a digestive or detoxifying role in the human small intestine and kidney, as well as functioning to activate angiotensin I.