Fig. 3.

SGLT2i can improve vasodilatory functions through COX-2. In endothelial cells, SGLT2i inhibit the production of ROS-induced PGH2 by inhibiting COX-2 and reduce the production of PGE2 and TXA2 downstream of PGH2. In vascular smooth muscle, although PGE2 activates EP4 receptors to dilate blood vessels, TAX2 activates TP receptors to cause vasoconstriction. In addition, downstream EP4 can cascade into ERK1/2/NOX4 to produce ROS, which contributes to vasoconstriction and the activation of COX-2. In vascular smooth muscle, COX-2 activates and catalyses AA to produce PGH2, which constricts blood vessels