Abstract Body: Hypertension is an underlying contributor to adverse vascular outcomes, promoting cardiovascular disease progression in an estimated population of 1.4 billion adults. This significantly burdens healthcare systems and leads to excess mortality. Research addressing this issue is critical, but currently available models are ripe for improvement. We created the HA-AngII Adeno-Associated Virus (AAV), which induces sustained elevation of blood pressure (BP). The timing of blood pressure elevation is controllable, dependent on the administration of HA-AngII through retro-orbital injection. Using a liver-targeting AAV2/8 capsid, viral transduction results in a stable episome in hepatocytes. This leads to long term production and secretion of the AngII peptide. Circulating AngII activates the Angiotensin Type 1 (AT1) receptor, elevating BP in the animal. This approach combines the advantages of temporal control with long term expression, creating an improved model of chronic BP elevation. Furthermore, this model can be combined with genetic or surgical models to mimic hypertension comorbidities such as hyperlipidemia or obesity. The level of BP elevation in C57BL/6J mice was monitored through radiotelemetry. The role of AT1 receptors was validated through administration of the AT1 receptor blocker Losartan. Adaptations to chronic hypertension were investigated, demonstrating hypertrophy of the left ventricle and perivascular collagen deposition in the heart. Changes in vessel reactivity and mechanical properties were also investigated. Protein levels of AngII receptors AT1 and AT2 were evaluated in the aorta. Future studies will focus on adaptive changes in the kidneys and combined effects resulting from HA-AngII administration in hyperlipidemic models.