Mitochondrial Damage and Hypertension: Another Dark Side of Sodium Excess

Essential or primary hypertension (HT) is a worldwide health problem with no definitive cure. Although the exact pathogenesis of HT is not known, genetic factors, increased renin-angiotensin and sympathetic system activity, endothelial dysfunction, oxidative stress, and inflammation play a role in its development. Environmental factors such as sodium intake are also important for BP regulation, and excess sodium intake in the form of salt (NaCl, sodium chloride) increases blood pressure in salt-sensitive people. Excess salt intake increases extracellular volume, oxidative stress, inflammation, and endothelial dysfunction. Recent evidence suggests that increased salt intake also disturbs mitochondrial function both structurally and functionally which is important as mitochondrial dysfunction is associated with HT. In the current review, we have summarized the experimental and clinical data regarding the impact of salt intake on mitochondrial structure and function.

Excess salt intake damage mitochondrial structure (e.g., shorter mitochondria with less cristae, increased mitochondrial fission, increased mitochondrial vacuolization). Functionally, high salt intake impairs mitochondrial oxidative phosphorylation and electron transport chain, ATP production, mitochondrial calcium homeostasis, mitochondrial membrane potential, and mitochondrial uncoupling protein function. Excess salt intake also increases mitochondrial oxidative stress and modifies Krebs cycle protein expressions. Studies have shown that high salt intake impairs mitochondrial structure and function. These maladaptive mitochondrial changes facilitate the development of HT especially in salt-sensitive individuals. High salt intake impairs many functional and structural components of mitochondria. These mitochondrial alterations along with increased salt intake promote the development of hypertension.