Metabolism of angiotensin I in isolated rat hearts. Effect of angiotensin converting enzyme inhibitors.
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.
Neves
L A
LA
Departamento de Fisiologia e Biofisica, ICB-UFMG, Belo Horizonte, MG, Brazil.
Almeida
A P
AP
Khosla
M C
MC
Santos
R A
RA
D000803:Angiotensin I / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D008297:Male; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar
D000806:Angiotensin-Converting Enzyme Inhibitors; D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D000804:Angiotensin II; D000803:Angiotensin I