Septic shock remains an important issue for critical care physicians. Despite significant advances in the knowledge of its pathophysiology, new effective therapeutic approaches have yet to emerge. Consequently, research on its pathophysiology must be continued. In a recent study, Katharina Mederle and colleagues explored the impact of angiotensin 1 receptor-associated protein 1 (Arap1) deficiency on vascular hyporesponsiveness in an experimental model of septic shock. The authors demonstrate that experimental septic shock downregulates Arap1 expression, which in turn contributes to vascular hyporesponsiveness to angiotensin II.