Therapeutic time window for angiotensin‐(1–7) in acute lung injury

Background and Purpose There is presently no proven pharmacological therapy for the acute respiratory distress syndrome. Recently, we and others discovered that the heptapeptide angiotensin‐(1–7) [Ang‐(1–7)] shows significant beneficial effects in preclinical models of acute lung injury (ALI). Here, we aimed to identify the best time window for Ang‐(1–7) administration to protect rats from oleic acid (OA) induced ALI. Experimental Approach The effects of i.v. infused Ang‐(1–7) were examined over four different time windows before or after induction of ALI in male Sprague–Dawley rats. Haemodynamic effects were continuously monitored, and loss of barrier function, inflammation and lung peptidase activities were measured as experimental endpoints. Key Results Ang‐(1–7) infusion provided the best protection against experimental ALI when administered by continuous infusion starting immediately after 30 min OA infusion till the end of the experiment (30–240 min). Both pretreatment (−60 to 0 min before OA) and short‐term therapy (30–90 min) also had beneficial effects although less pronounced than the effects achieved with the optimal therapy window. Starting infusion of Ang‐(1–7) 60 min after the end of OA treatment (90–240 min) did not protect barrier function or haemodynamics but still reduced myeloperoxidase activity and increased ACE2/ACE activity ratio respectively. Conclusions and Implications Our findings indicate that early initiation of therapy after ALI and continuous drug delivery are most beneficial for optimal therapeutic efficiency of Ang‐(1–7) treatment in experimental ALI and, presumably accordingly, in clinical acute respiratory distress syndrome.