Sustained Exposure to the SGLT2 Inhibitor Ertugliflozin, but Not NHE‐1 Inhibition by Cariporide, Attenuates Adrenergic Stimulation of Cytosolic CA2+ Levels in Spontaneously Contracting Cardiac Myocytes

Inhibitors of sodium‐glucose cotransporter 2 (SGLT2i) target renal SGLT2 to reduce reabsorption of glucose, facilitate urinary glucose excretion, and lower blood glucose levels in patients with Type II diabetes (T2DM). The drugs, however, also decrease mortality and heart failure (HF) hospitalizations in T2DM patients. Patients with HF exhibit sympathetic overdrive and cytosolic Ca2+ overload in cardiac myocytes. Because SGLT2i harbor cardioprotective effects, we hypothesize that the SGLT2i ertugliflozin (ERTU) will lower cytosolic Ca2+ concentration ([Ca2+]cyt) in metabolically active and contracting cardiac myocytes after adrenergic stimulation.