Angiotensin II formation in the intact human heart. Predominance of the angiotensin-converting enzyme pathway

L. S. Zisman, W. T. Abraham, G. E. Meixell, B. N. Vamvakias, R. A. Quaife, B. D. Lowes, R. L. Roden, S. J. Peacock, B. M. Groves, M. V. Raynolds, M. R. Bristow, M. B. Perryman

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116 Scopus citations

Abstract

It has been proposed that the contribution of myocardial tissue angiotensin converting enzyme (ACE) to angiotensin II (Ang II) formation in the human heart is low compared with non-ACE pathways. However, tittle is known about the actual in vivo contribution of these pathways to Ang II formation in the human heart. To examine angiotensin II formation in the intact human heart, we administered intracoronary 123I-labeled angiotensin I (Ang 1) with and without intracoronary enalaprilat to orthotopic heart transplant recipients. The fractional conversion of Ang I to Ang II, calculated after separation of angiotensin peptides by HPLC, was 0.415 ± 0.104 (n = 5, mean ± SD). Enalaprilat reduced fractional conversion by 89%, to a value of 0.044 ± 0.053 (n = 4, P = 0.002). In a separate study of explanted hearts, a newly developed in vitro Ang II-forming assay was used to examine cardiac tissue ACE activity independent of circulating components. ACE activity in solubilized left ventricular membrane preparations from failing hearts was 49.6 ± 5.3 fmol 125I-Ang II formed per minute per milligram of protein (n = 8, ± SE), and 35.9 ± 4.8 fmol/min/mg from nonfailing human hearts (n = 7, P = 0.08). In the presence of 1 μM enalaprilat, ACE activity was reduced by 85%, to 7.3 ± 1.4 fmol/min/mg in the failing group and to 4.6 ± 1.3 fmol/min/mg in the nonfailing group (P < 0.001). We conclude that the predominant pathway for angiotensin II formation in the human heart is through ACE.

Original languageEnglish (US)
Pages (from-to)1490-1498
Number of pages9
JournalJournal of Clinical Investigation
Volume96
Issue number3
DOIs
StatePublished - 1995

Keywords

  • angiotensin I
  • angiotensin-converting enzyme inhibitors
  • cardiomyopathy
  • peptidyl dipeptidase A
  • renin-angiotensin system

ASJC Scopus subject areas

  • Medicine(all)

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    Zisman, L. S., Abraham, W. T., Meixell, G. E., Vamvakias, B. N., Quaife, R. A., Lowes, B. D., Roden, R. L., Peacock, S. J., Groves, B. M., Raynolds, M. V., Bristow, M. R., & Perryman, M. B. (1995). Angiotensin II formation in the intact human heart. Predominance of the angiotensin-converting enzyme pathway. Journal of Clinical Investigation, 96(3), 1490-1498. https://doi.org/10.1172/JCI118186