Metabolism of angiotensin I in isolated rat hearts. Effect of angiotensin converting enzyme inhibitors

Biochem Pharmacol. 1995 Oct 26;50(9):1451-9. doi: 10.1016/0006-2952(95)02049-7.

Abstract

In this study, the formation of biologically active angiotensins from angiotensin I (Ang I) in isolated rat hearts was evaluated. The role of angiotensin converting enzyme (ACE) in Ang I metabolism was also investigated. HPLC analysis of heart perfusate showed that 125I-Ang I was metabolized extensively (single passage) in the rat coronary circulation in vitro leading to the formation of the biologically active angiotensins: angiotensin II (Ang II), Ang-(2-8), Ang-(3-8) and Ang-(1-7). Ang II was the major product identified in HPLC fractions, corresponding to 7.8 +/- 0.89% of the total radioactivity recovered. A similar profile was observed when single-passage metabolism of non-isotopic Ang I was evaluated by HPLC, followed by radioimmunoassay of the eluate fractions. When 125I-Ang I was perfused in the presence of ACE inhibitors (enalaprilat, ramiprilat) in concentrations up to 130 microM, the formation of Ang II was only partially inhibited (approximately 50%). A similar tendency was observed for Ang-(2-8), Ang-(3-8) and Ang-(2-7). The formation of Ang-(1-7) and its related fragments Ang-(3-7) and Ang-(4-7) was not changed significantly by ACE inhibitors, although a slight increase in formation of these fragments was observed. No significant changes were observed for the carboxyl-terminal fragments of Ang I: Ang-(2-10), Ang-(3-10), and Ang-(4-10). The fractional metabolism of Ang I was not modified by ACE inhibition. These findings suggest that biologically active angiotensins can be formed from Ang I in the rat coronary circulation. These locally generated peptides may contribute to the actions of the renin-angiotensin system in the heart.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin I / metabolism*
  • Angiotensin II / metabolism
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Heart / drug effects*
  • In Vitro Techniques
  • Iodine Radioisotopes
  • Male
  • Myocardium / enzymology
  • Myocardium / metabolism*
  • Peptide Fragments / metabolism
  • Radioimmunoassay
  • Rats
  • Rats, Wistar

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Iodine Radioisotopes
  • Peptide Fragments
  • Angiotensin II
  • Angiotensin I