Metabolism of Angiotensin-(1–7) by Angiotensin-Converting Enzyme

Abstract

Angiotensin converting enzyme (ACE) inhibitors augment circulating levels of the vasodilator peptide angiotensin-(1–7) [Ang-(1–7)] in man and animals. Increased concentrations of the peptide may contribute to the antihypertensive effects associated with ACE inhibitors. The rise in Ang-(1–7) following ACE inhibition may result from increased production of the peptide or inhibition of the metabolism of Ang-(1–7)-similar to that observed for bradykinin. To address the latter possibility, we determined whether Ang-(1–7) is a substrate for ACE in vitro. In a pulmonary membrane preparation, the ACE inhibitor lisinopril attenuated the metabolism of low concentrations of 125I-Ang-(1–7). The primary product of 125I-Ang-(1–7) metabolism was identified as Ang-(1–5). Using affinity-purified ACE from canine lung, HPLC separation and amino acid analysis revealed that ACE functioned as a dipeptidyl carboxypeptidase cleaving Ang-(1–7) to the pentapeptide Ang-(1–5). The ACE inhibitors lisinopril and enalaprilat (1 μmol/L)...