Na⁺/H⁺ exchangers: Physiology and link to hypertension and organ ischemia

Purpose of review: Na⁺/H⁺ exchangers (NHEs) are ubiquitous proteins with a very wide array of physiological functions, and they are summarized in this paper in view of the most recent advances. Hypertension and organ ischemia are two disease states of paramount importance in which NHEs have been implicated. The involvement of NHEs in the pathophysiology of these disorders is incompletely understood. This paper reviews the principal findings and current hypotheses linking NHE dysfunction to hypertension and ischemia. Recent findings: With the advent of large-scale sequencing projects and powerful in-silico analyses, we have come to know what is most likely the entire mammalian NHE gene family. Recent advances have detailed the roles of NHE proteins, exploring new functions such as anchoring, scaffolding and pH regulation of intracellular compartments. Studies of NHEs in disease models, even though not conclusive to date, have contributed new evidence on the interplay of ion transporters and the delicate ion balances that may become disrupted. Summary: This paper provides the interested reader with a concise overview of NHE physiology, and aims to address the implication of NHEs in the pathophysiology of hypertension and organ ischemia in light of the most recent literature.