Inhibition of erythrocyte anion exchange by tolrestat, an inhibitor of aldose reductase

Abstract

Tolrestat, and aldose-reductase inhibitor, was shown to be a rapid and potent inhibitor of chloride exchange on the band 3 protein of human erythrocytes. Tolrestat binds to a site distinct from the chloride transport site and binds to one half of the transporters at 5 × 10 −7 mol/L in the absence of chloride and at 3.6 × 10 −5 mol/L in physiologic chloride concentrations. Although these concentrations are 20- to 1,000-fold greater than the IC 50 for aldose-reductase inhibition by tolrestat, they are achieved during routine pharmacologic therapy in humans. Consequently, Cl HCO 3 exchange rates may be reduced, and there may be decreased CO 2 clearance from coronary and respiratory center capillary beds and inappropriate hyperpnea. There also may be transitory intracellular alkalinization in cells with a Cl HCO 3 exchanger in their plasma membrane.