Background: Angiotensin II type 1 receptor (AT 1 R) autoantibody (AT1-AA) was first identified as a causative factor in preeclampsia. Unlike physiological ligand angiotensin II (Ang II), AT1-AA can induce vasoconstriction in a sustained manner, causing a series of adverse effects, such as vascular injury and poor placental perfusion. However, its underlying mechanisms remain unclear. Here, from the perspective of AT 1 R internalization, the present study investigated the molecular mechanism of sustained vasoconstriction induced by AT 1 R autoantibody. Methods and Results: In the current study, we used the vascular-ring technique to determine that AT1-AA-positive IgG, which was obtained from the sera of preeclamptic patients, induced long-term vasoconstriction in endothelium-intact or endothelium-denuded rat thoracic arteries. The effect was caused by prolonged activation of AT 1 R downstream signals in vascular smooth muscle cells, including Ca 2+ , protein kinase C, and extracellular signal-regulated kinase 1 and 2. Then, using subcellular protein fractionation, cell surface protein biotinylation, and total internal reflection fluorescence, we found that AT1-AA-positive IgG resulted in significantly less AT 1 R internalization than in the Ang II treatment group. Moreover, through use of fluorescent tracing and bioluminescence resonance energy transfer, we found that AT1-AA-positive IgG cannot induce the recruitment of β-arrestin1/2, which mediated receptor internalization. Then, the effect of sustained AT 1 R activation induced by AT1-AA-positive IgG was rescued by overexpression of β-arrestin2. Conclusions: These data suggested that limited AT 1 R internalization resulting from the inhibition of β-arrestin1/2 recruitment played an important role in sustained vasoconstriction induced by AT1-AA-positive IgG, which may set the stage for avoiding AT 1 R overactivation in the management of preeclampsia. ? 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.