ACE2 and angiotensin 1-7 are increased in a human model of cardiovascular hyporeactivity: pathophysiological implications.
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.
Calò
Lorenzo A
LA
Department of Clinical and Experimental Medicine, Medical Clinic 4, University of Padua, Padua, Italy. renzcalo@unipd.it
Schiavo
Silvia
S
Davis
Paul A
PA
Pagnin
Elisa
E
Mormino
Paolo
P
D'Angelo
Angela
A
Pessina
Achille C
AC
D000803:Angiotensin I / Q000097:blood / Q000502:physiology*; D000085962:Angiotensin-Converting Enzyme 2; D001477:Bartter Syndrome / Q000097:blood / Q000503:physiopathology*; D005260:Female; D053579:Gitelman Syndrome / Q000097:blood / Q000503:physiopathology*; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000503:physiopathology*; D008297:Male; D010446:Peptide Fragments / Q000097:blood / Q000502:physiology*; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000502:physiology*
D010446:Peptide Fragments; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7)