Angiotensin-converting enzyme substrates hydrolyzed by fibroblasts and vascular endothelial cells

Abstract

Angiotensin-converting enzyme (ACE, E.C. 3.4.15.1) activity has been documented in eight cultures of fibroblasts with the ACE substrates benzoyl-phe-ala-pro and hippuryl-his-leu. Hydrolysis of these ACE substrates by fibroblasts is inhibited by SQ-14225 and SQ-20881, specific inhibitors of ACE activity, and by EDTA. However, ACE activity in seven of eight cultures of fibroblasts tested is less than ACE activity in two cultures of vascular endothelial cells. The rats of hydrolysis of benzoyl-phe-ala-pro by fibroblasts and by endothelial cells differ at high substrate concentrations; therefore, the ACE activity in fibroblasts may be due to either a different isoenzyme of ACE of a different accessibility to substrate. Production of angiotensin II from angiotensin I is documented in cultures of vascular endothelial cells but not in cultures of fibroblasts, however, angiotensin II is further degraded by fibroblasts and not by endothelial cells.