NOS3 and endothelial dysfunction: Several experimental studies have also demonstrated that the BP lowering effects of SGLT2 inhibition may be mediated by mechanisms unrelated to glycosuria: e.g., by reducing arterial stiffness [88]; to an improvement in endothelial dysfunction [89] or the influence they would have on the activity of endothelial nitric oxide synthase, in particular endothelial nitric oxide synthase, by remodulating NO synthesis and normalizing vascular tone.