Pre-treatment with the angiotensin receptor 1 blocker losartan protects renal blood flow and oxygen delivery after propofol-induced hypotension in pigs

Abstract

Hypotensive events are strongly correlated to the occurrence of perioperative acute kidney injury, but the underlying mechanisms for this are not completely elucidated. We hypothesised that anaesthesia-induced hypotension causes renal vasoconstriction and decreased oxygen delivery via angiotensin II-mediated renal vasoconstriction. Pigs were anaesthetised, surgically prepared and randomised to vehicle/losartan treatment (0.15 mg*kg ⁻¹). A deliberate reduction in arterial blood pressure was caused by infusion of propofol (30 mg*kg ⁻¹) for 10 min. Renal function and haemodynamics were recorded 60 min before and after hypotension. Propofol induced hypotension in all animals ( p < 0.001). Renal blood flow (RBF) and renal oxygen delivery (RDO ₂) decreased significantly regardless of treatment but more so in vehicle-treated compared to losartan-treated ( p = 0.001, p = 0.02, respectively). During recovery RBF and RDO ₂ improved to a greater extent in the losartan-treated compared to vehicle-treated (+ 28 ml*min ⁻¹, 95%CI 8–50 ml*min ⁻¹, p = 0.01 and + 3.1 ml*min ⁻¹, 95%CI 0.3–5.8 ml*min ⁻¹, p = 0.03, respectively). Sixty minutes after hypotension RBF and RDO ₂ remained depressed in vehicle-treated, as renal vascular resistance was still increased ( p < 0.001). In losartan-treated animals RBF and RDO ₂ had normalised. Pre-treatment with losartan improved recovery of renal blood flow and renal oxygen delivery after propofol-induced hypotension, suggesting pronounced angiotensin II-mediated renal vasoconstriction during blood pressure reductions caused by anaesthesia.