Abstract 12295: Vascular Response to the Sodium-Glucose Cotransporter Inhibitor in Type 2 Diabetic Mice

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of oral drugs for the treatment of type 2 diabetes (T2D) and they reduce plasma blood glucose levels by inhibiting renal glucose reabsorption. However, there are no data investigating the vascular response to the SGLT inhibitors. This study is designed to determine whether and how phlorizin (a non-specific SGLT1 and 2 inhibitor) and canagliflozin, a FDA-approved SGLT2-specific inhibitor, regulate vascular tone in pulmonary and coronary arteries of control and T2D mice. Both phlorizin and canagliflozin induced vascular relaxation in pre-contracted pulmonary and coronary arteries. In addition, pretreatment of SGLT inhibitors significantly attenuated NO-dependent vascular relaxation in pulmonary arteries (assessed by sodium nitroprusside, a NO donor), but not in coronary arteries. We further examined the downstream of NO-dependent relaxation in pulmonary artery using a cGMP analogue and a phosphodiesterase inhibitor as well as measured membran...