ACE2 and angiotensin 1-7 are increased in a human model of cardiovascular hyporeactivity: pathophysiological implications

J Nephrol. 2010 Jul-Aug;23(4):472-7.


Background: ACE and ACE2 produce angiotensin II (Ang II), a vasopressor that induces cardiovascular remodeling, and Ang 1-7, a vasodilator with an antiremodeling effect. While Ang 1-7 has antiarrhythmic properties, at higher concentration it may induce ventricular tachycardia and sudden death. ACE2, therefore, may play an essential role in blood pressure homeostasis, in the long-term complications of hypertension (cardiovascular remodeling), and in the induction of cardiac electric abnormalities. This study evaluated the levels of ACE2 and Ang 1-7 in Bartter's/Gitelman's patients (BS/GS) who have elevated Ang II and endogenous blockade of Ang II type 1 receptor signaling compared with healthy subjects (C) and essential hypertensives (EH). BS/ GS patients were also considered because of their predisposition to cardiac arrhythmias, which has yet to be completely clarified.

Methods: Mononuclear cell ACE2 and Ang 1-7 were evaluated using western blot.

Results: One-way ANOVA showed that ACE2 and Ang 1-7 levels were significantly different between the three groups (p=0.0074 and p=0.0001, respectively). Post-hoc analysis (Tukey's HSD) showed that both ACE2 (1.59+/-0.63) and Ang1-7 (2.26+/-1.18) were significantly elevated in BS/GS compared with either C (0.98+/-0.45; p=0.008; 1.12+/-0.48, p=0.002, respectively) or EH (1.06+/-0.24; p=0.043; 0.72+/-0.28; p=0.0001, respectively). ACE2 and Ang 1-7 directly correlated only in BS/GS (r=0.91, p<0.0003).

Conclusions: The elevated ACE2 and Ang 1-7 in BS/ GS patients mirror those in hypertensives and are in line with the clinical, hemodynamic and pathophysiological characteristics of BS/GS, likely contributing to them. In consideration of the clinical picture of these syndromes, the opposite of hypertension, the results of this study further strengthen the importance of the ACE2/Ang 1-7 system in the regulation of vascular tone and cardiovascular biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin I / blood
  • Angiotensin I / physiology*
  • Angiotensin-Converting Enzyme 2
  • Bartter Syndrome / blood
  • Bartter Syndrome / physiopathology*
  • Female
  • Gitelman Syndrome / blood
  • Gitelman Syndrome / physiopathology*
  • Humans
  • Hypertension / blood
  • Hypertension / physiopathology*
  • Male
  • Peptide Fragments / blood
  • Peptide Fragments / physiology*
  • Peptidyl-Dipeptidase A / blood
  • Peptidyl-Dipeptidase A / physiology*


  • Peptide Fragments
  • Angiotensin I
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • angiotensin I (1-7)