Na⁺-H⁺ Exchanger and Its Role in Essential Hypertension and Diabetes Mellitus

The Na⁺-H⁺ exchanger is a ubiquitous transport system that is involved in the regulation of intracellular pH, cell growth and proliferation, cell volume regulation, and transepithelial absorption of Na⁺, Cl^-, and HCO₃^-. Altered activity of the Na⁺-H⁺ exchanger has been implicated as a mechanism contributing to the development of high blood pressure in subgroups of patients with essential hypertension and in various animal models of hypertension. Many of these studies measured Na⁺-Li⁺ exchange rather than Na⁺-H⁺ exchange, hypothesizing that Na⁺-Li⁺ exchange represents a functional mode of the Na⁺-H⁺ exchanger. However, this is a controversial assumption. Several studies have also shown an association between erythrocyte Na⁺-Li⁺–exchange rate and predisposition to nephropathy in patients with insulin-dependent diabetes mellitus. The recent cDNA cloning of at least one isoform of the Na⁺-H⁺ exchanger will help clarify the cellular mechanisms of regulation of the exchanger and its possible role in pathophysiological states such as hypertension.