Gitelman's and Bartter's Syndromes: From Genetics to the Molecular Basis of Hypertension and More

BACKGROUND: Gitelman's and Bartter's syndromes (GS/BS) are rare genetic tubulopathies characterized by electrolyte imbalance and activation of the renin-angiotensin-aldosterone system (RAAS). These syndromes have intriguing biochemical and hormonal abnormalities that lead them to be protected from hypertension and cardiovascular and renal remodeling. SUMMARY: In this review, we explore the biochemical/molecular mechanisms induced by the activation of the RAAS and its counterregulatory arm which is particularly activated in GS/BS patients, in the context of blood pressure regulation. In addition, we report our findings in the context of the COVID-19 pandemic where we observed GS/BS subjects being protected from infection. KEY MESSAGES: The intracellular pathways induced by Ang II, starting from induction of oxidative stress and vasoconstriction, are crucial for the progression toward cardiovascular-renal remodeling and might be useful targets in order to reduce/halt the progression of Ang II/oxidative stress-induced cardiovascular-renal morbidity in several diseases.