Reactive oxygen species (ROS) are intermediates in reduction-oxidation reactions that begin with the addition of one electron to molecular
oxygen, generating the primary ROS
superoxide, which in turn interacts with other molecules to produce secondary ROS, such as
hydrogen peroxide,
hydroxyl radical, and
peroxynitrite. ROS are continuously produced during metabolic processes and are deemed to play an important role in
cardiovascular diseases, namely, myocardial
hypertrophy and
fibrosis and
atherosclerosis, via oxidative damage of
lipids,
proteins, and
deoxyribonucleic acid.
Angiotensin II (Ang II) is a potent vasoactive agent that also exerts mitogenic, proinflammatory, and profibrotic effects through several signaling pathways, in part involving ROS, particularly
superoxide and
hydrogen peroxide. Moreover, Ang II stimulates
NADPH oxidases, leading to higher ROS generation and oxidative stress. Bartter/
Gitelman syndrome patients, despite elevated plasma
renin activity, Ang II, and
aldosterone levels, exhibit reduced peripheral resistance, normal/
low blood pressure, and blunted pressor effect of
vasoconstrictors. In addition, notwithstanding the activation of the renin-angiotensin system and the increased plasma levels of Ang II, these patients display decreased production of ROS, reduced oxidative stress, and increased
antioxidant defenses. In fact, Bartter/
Gitelman syndrome patients are characterized by reduced levels of p22(
phox) gene expression and undetectable plasma
peroxynitrite levels, while showing increased plasma
antioxidant power and expression of
antioxidant enzymes, such as
heme oxygenase-1. In conclusion, multifarious data suggest that Bartter and
Gitelman syndrome patients are a model of low oxidative stress and high
antioxidant defenses. The contribution offered by the study of these syndromes in elucidating the molecular mechanisms underlying this favorable status could offer chances for new therapeutic targets in disease characterized by high levels of
reactive oxygen species.