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 (RDO2) 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 RDO2 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 RDO2 remained depressed in vehicle-treated, as renal vascular resistance was still increased (p < 0.001). In losartan-treated animals RBF and RDO2 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.

Prevention of hemorrhage-induced renal vasoconstriction and hypoxia by angiotensin II type 1 receptor antagonism in pigs

“…1]. In accordance to our recently published porcine study, losartan infusion had no significant effect on baseline variables (26). Hypotensive hemorrhage caused a transient decrease in urine output in the losartan-treated [À1.5 (CI: 0.7-2.4) mL•min À1 , P = 0.02, Table 1] but not in the vehicle-treated animals (P = 0.30).…”

“…Renal vascular beds seem more susceptible than the heart, brain and skeletal muscle to ANG II-mediated effects (63). From a renal perspective, the current data and previous reports suggest that ANG II per se might do more harm than is usually acknowledged in susceptible high-risk individuals when exposed to anesthesiaand hemorrhage-induced hypotensive events (26). Congruent with this hypothesis studies have reported that continuing preoperative ANG II inhibition is imperative to reduce postoperative morbidity and mortality (64,65).…”

“…We have recently demonstrated that AT 1 R blockade improves renal perfusion and oxygenation after transient hypotension due to an exaggerated dose of anesthetics (26). The present study examined the renal effects of AT 1 R blockade during hypotensive hemorrhage in a large animal model.…”

“…Vehicle-treated animals received additional Ringer acetate equal to the volume of administered losartan. We have in a previous pig-study investigated the blockade of ANG II after anesthesia-induced hypotension (26). Here, we anticipated that prolonged hemorrhage would increase plasma levels of ANG II to higher levels and therefore increased the dose of losartan tenfold.…”

Anesthesia and the renal sympathetic nervous system in perioperative AKI

“…10 If the arterial blood pressure falls below the autoregulatory threshold, RBF is reduced in parallel to the reduction in pressure. 11,12 Even short-term hypotension (1−5 minutes) with mean arterial pressure below 55 mmHg has been associated with increased incidence of postoperative AKI. 9 It remains unclear how RBF and the autoregulatory threshold in humans is affected by anesthesia, but it is likely that major reductions in arterial blood pressure significantly impair RBF.…”