Angiotensin-(1-12): A Chymase-Mediated Cellular Angiotensin II Substrate

  • Sarfaraz Ahmad
  • Jasmina Varagic
  • Leanne Groban
  • Louis J Dell’Italia
  • Sayaka Nagata
  • Neal D. Kon
  • Carlos M. Ferrario
Hypertension and the Kidney(R Carey, Section Editor)

DOI: 10.1007/s11906-014-0429-9

Cite this article as:
Ahmad, S., Varagic, J., Groban, L. et al. Curr Hypertens Rep (2014) 16: 429. doi:10.1007/s11906-014-0429-9
Part of the following topical collections:
  1. Topical Collection on Hypertension and the Kidney

Abstract

The classical view of biochemical pathways for the formation of biologically active angiotensins continues to undergo significant revision as new data uncovers the existence of important species differences between humans and rodents. The discovery of two novel substrates that, cleaved from angiotensinogen, can lead to direct tissue angiotensin II formation has the potential of radically altering our understanding of how tissues source angiotensin II production and explain the relative lack of efficacy that characterizes the use of angiotensin converting enzyme inhibitors in cardiovascular disease. This review addresses the discovery of angiotensin-(1-12) as an endogenous substrate for the production of biologically active angiotensin peptides by a non-renin dependent mechanism and the revealing role of cardiac chymase as the angiotensin II convertase in the human heart. This new information provides a renewed argument for exploring the role of chymase inhibitors in the correction of cardiac arrhythmias and left ventricular systolic and diastolic dysfunction.

Keywords

Angiotensin-(1-12) Angiotensin II Angiotensin-(1-7) Cardiac chymase Angiotensin-converting enzyme Metabolism Renin-angiotensin system Angiotensinogen 

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Sarfaraz Ahmad
    • 1
  • Jasmina Varagic
    • 1
    • 2
    • 3
  • Leanne Groban
    • 2
    • 4
  • Louis J Dell’Italia
    • 7
  • Sayaka Nagata
    • 1
  • Neal D. Kon
    • 5
  • Carlos M. Ferrario
    • 1
    • 3
    • 6
  1. 1.Division of Surgical SciencesWake Forest School of MedicineWinston SalemUSA
  2. 2.Hypertension and Vascular Research CenterWake Forest School of MedicineWinston SalemUSA
  3. 3.Department of Physiology/PharmacologyWake Forest School of MedicineWinston SalemUSA
  4. 4.Department of AnesthesiologyWake Forest School of MedicineWinston SalemUSA
  5. 5.Cardiothoracic SurgeryWake Forest School of MedicineWinston SalemUSA
  6. 6.Department of Internal Medicine/NephrologyWake Forest School of MedicineWinston SalemUSA
  7. 7.Division of Cardiovascular Disease, Department of MedicineUniversity of Alabama Medical Center and Birmingham VA Medical CenterBirminghamUSA

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