Key result
Bartter's and Gitelman's syndromes are linked to ~62% higher mononuclear cell ACE2 levels.
Why the study?
The role of ACE2 and Ang 1-7 in blood pressure homeostasis, cardiovascular remodeling, and cardiac electric abnormalities in Bartter's/Gitelman's patients compared with healthy subjects and hypertensives was unclear.
Observational
Absolute Event Rate: 1.59% vs 0.98%
p-value: p=0.008
Should not change management in these rare syndromes; leaves open whether ACE2/Ang 1-7 upregulation extends to common cardiovascular states.
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.
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Calò et al. (2010) conducted an observational in Bartter's/Gitelman's syndrome. Bartter's/Gitelman's syndrome vs. Healthy subjects and essential hypertensives was evaluated on Mononuclear cell ACE2 level (p=0.008). Mononuclear cell ACE2 (1.59 vs 0.98; P=0.008) and Ang 1-7 (2.26 vs 1.12; P=0.002) levels were significantly elevated in patients with Bartter's/Gitelman's syndrome compared to healthy subjects.
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