Background: The angiotensin II type 1 (AT1) receptor has a relevant role in the physiology and pathophysiology of the cerebrovascular system. Its vasoconstrictor effect, consecutive to Gq protein activation, reduces cerebral perfusion during stroke. In addition, AT1 receptor activity is directly regulated by the β-arrestin pathway, involved in receptor internalization [1]. Recently, the development of biased agonists, able to selectively activate the β-arrestin pathway without Gq activation appears to be a promising new therapeutic strategy in cardiovascular pathologies [2]. In the current project, we explore the impact of an AT1 biased agonist (TRV027) on the regulation of the cerebral circulation. Methods: We evaluated the TRV027 signaling on HEK293-cells overexpressing AT1 using bioluminescence resonance energy transfer (NanoBRET) and calcium mobilization assays. In parallel, concentration-response curves to TRV027 were built on an ex vivo model of isolated and perfused middle cerebral arteries (MCA) by measuring changes in internal diameter. Results: BRET results show that TRV027 induces an activation of the β-arrestin pathway with a maximal increase of BRET ratio of 0.08 while inactivating the Gq pathway. Calcium mobilization assays confirm this Gq inactivation. As expected, results obtained in MCA show no effect of TRV027 on arterial diameter. Discussion: Tracking the AT1 receptor using specific fluorescent tools to follow its internalization (confocal microscopy) is currently under development. The next step will be to assess in vivo the potential beneficial and protective effects of TRV027 in cerebrovascular pathologies, in collaboration with Maastricht University. 1.Violin JD and Lefkowitz RJ. Pharmacological Sciences Vol.28 No.8 2.Boerrigter, Soergel, Violin, et al. Circ Heart Fail, 2012. 5: 627-634