Does the cardioprotective effect of Empagliflozin involve inhibition of the sodium-proton exchanger?
Abstract
This editorial refers to ‘Off-target effects of SGLT2 blockers: empagliflozin does not inhibit Na+/H+ exchanger-1 or lower [Na+]i in the heart’ by Y.J. Chung et al., pp. 2794–2806. Sodium glucose transport 2 inhibitors, such as empagliflozin (EMPA), inhibit glucose re-absorption by the kidney and have been developed to reduce plasma glucose levels in diabetic patients. However, studies have suggested that these drugs have cardioprotective benefits, independent of their effect on plasma glucose.1 Several possibilities have been proposed to explain these cardioprotective effects including effects on metabolism, weight loss, alterations in EPO, and inhibition of plasma membrane sodium-proton exchanger (NHE). As reviewed by Vaughan-Jones et al.2 intracellular pH is regulated by a series of acid extruding transporters including NHE and the Na+-bicarbonate cotransporter (NBC). There are also two acid loading proteins, the Cl−-bicarbonate exchange and Cl−-hydroxide exchange (CHE). Inhibition of NHE before ischaemia has been shown to reduce Na+ overload during ischaemia which in turn reduces Ca2+ entry into the myocyte via plasma membrane sodium-calcium exchange. However, a large clinical trial using cariporide, a specific NHE inhibitor, did not show protection in myocardial infarction patients, likely because the increase in myocardial Na+ and Ca2+ occurred before administration of the inhibitor at reperfusion. Zuurbier et al. reported that EMPA inhibits NHE and have proposed that…
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