SGLT inhibitors attenuate NO-dependent vascular relaxation in mouse pulmonary artery (677.3)

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of oral drugs for the treatment of type 2 diabetes and they reduce plasma blood glucose levels by inhibiting renal glucose reabsorption. However, there are no data focusing on microvascular or cardiovascular outcomes. The present study is designed to determine whether SGLT inhibitors, phlorizin (nonspecific SGLT1/SGLT2 inhibitor) and canagliflozin (SGLT2 specific inhibitor), regulate vascular relaxation in mouse coronary and pulmonary arteries. Isometric tension experiments were performed to evaluate vascular function. Phlorizin significantly decreased sodium nitroprusside (SNP, NO donor)-dependent vascular relaxation in pulmonary arteries; however phlorizin did not alter SNP-dependent relaxation in coronary arteries. Contrary to our expectation, phlorizin had no effect on either 8-Bromo-cGMP (a cell-permeable cGMP analogue) or papaverine (phosphodiesterase inhibitor)-induced relaxation in mouse pulmonary arteries. Canagliflozin inhibited S...