AGTR1 and hypertensive disorder: Indeed, in the hypertension model, circulating Ang II was shown to activate AT1R expressed in cerebral endothelial cells, modifying tight junctions and increasing transcytosis, which facilitated the entrance of blood-borne peptides into the PVS and activated AT1R in PVM.66 The downstream NADPH oxidase 2 (Nox2) elevation further exacerbated vascular oxidative stress, bringing about endothelial and PVM dysfunction and BBB leakage (Fig. 3D).