Direct effects of endotoxin on the function of the isolated perfused rat kidney

Direct effects of endotoxin on the function of the isolated perfused rat kidney. When the endotoxin-lipopolysaccharide (LPS) derived from the cell wall of gram-negative bacteria is given to the rat in vivo, there are prompt, marked decreases in glomerular filtration rate (GFR), renal blood flow (RBF) and % Na+ reabsorption (%T-Na+). However, it has not been determined whether the endotoxin itself has a direct effect on these renal functions. To test whether endotoxin has a direct renal effect, isolated rat kidneys (N = 8) were perfused for 160 minutes with a Krebs-Ringer-HCO3− solution containing substrate-free albumin (40 g/liter), glucose (5mM) and L(+) lactate (7.5mM). After control observations (20 to 80 min) were made, purified LPS from E. coli was added (TV = 4) to the perfusate to achieve [endotoxin] of 0.01 µg/ml (80 to 120 min) and 0.1 µg/ml (120 to 160 min). Endotoxin had no effect on GFR, Na+ reabsorption or tissue K+ content when compared to timed-control perfusions (N = 4). There was a small (∼10%) but significant decrease in mean perfusion flow rate (PFR) at the highest [endotoxin] when compared to the low [endotoxin]p but no change in GFR occurred. When the same LPS was given to four rats in vivo at a dose which achieved an [endotoxin] of ∼0.08 µg/ml plasma, there were prompt decreases in GFR and %T-Na+ and an increase in body temperature when compared with timed-controls; there also was a large loss of K+ from the kidney tissue. We conclude that endotoxin at a perfusate concentration which reduces GFR and %T-Na+, and causes a large loss of renal tissue K+ content in vivo, has no direct effect on these renal functions; mediators which are released extrarenally are apparently required to initiate the changes in renal function observed during endotoxemia in vivo