3.2 Restoration of NO by SGLT-2i’s
In vivo studies showed that SGLT-2i’s restored the endothelium-dependent vasodilation in both hyperglycaemic and euglycaemic animals (Salim et al. , 2016; Sayour et al. , 2019). Additionally, in vitro studies showed that EMPA and DAPA reverted the loss of NO in human ECs exposed to TNF-α (Uthman et al. , 2019; Juni et al. , 2021). However, phosphorylation of eNOS at Ser1177 in isolated ECs was not affected by EMPA, the rescued NO bioavailability in isolated human ECs was most likely mediated by the ROS inhibitory capacity of SGLT-2i’s (Uthman et al. , 2019; Juniet al. , 2021). In contrast, EMPA promoted eNOS phosphorylation via activating AMPK in ECs isolated from mice (Zhou et al. , 2018), which could be partially explained by species difference. Moreover, the studies of Uthman and Juni were performed within static ECs (Uthman et al. , 2019; Juni et al. , 2021). A further improvement in cellular studies could be the incorporation of dynamically activated ECs.