Renal sodium reabsorption, oxygen consumption, and gamma-glutamyltransferase excretion in the postischemic rat kidney.

The effect of 30 min of renal artery occlusion on renal sodium reabsorption, oxygen consumption, and brush border integrity was studied in the immediate 1-h reflow period. Rats were studied using clearance and renal extraction measurements. Glomerular filtration rate and renal plasma flow were measured over four consecutive 15-min periods; renal venous samples were drawn via an indwelling catheter. Renal oxygen consumption (QO2) was calculated from renal blood flow, corrected for urine flow, and from blood oxygen content measured with a fuel cell analyzer. Brush border integrity was assessed by the excretion of the brush border marker enzyme gamma-glutamyltransferase as well as by morphologic observation. Ischemia induced a 10-fold rise in fractional sodium excretion in the initial 0- to 15-min period, rose to 20-fold during the subsequent two periods, 15-45 min, and then returned to the initial reflow period level. The progressive deterioration of renal function with reflow could not be attributed to an increase in the filtered Na+ load. Rather, Na+ reabsorption appeared to be related to the presence of intact brush borders at 0-15 min, their removal from the luminal surface between 15 and 45 min, and their return at 60 min of reflow. Renal QO2 was coupled to Na+ reabsorption in the initial 15-min and final 45- to 60-min reflow periods. However QO2 was significantly increased over the control level at 30-45 min of reflow. The results point to a significant role of brush border uptake in the development of functional impairment following renal ischemia and suggest that the associated rise in renal O2 consumption may be coupled to the reparation of this organelle.

Ammonia production and pathways of glutamine utilization in rat kidney slices.

Ammonia production from glutamine was studied in slices from non-acidotic and acidotic rat kidneys. Slices from non-acidotic kidneys made 53% as much ammonia from D-glutamine as from L-glutamine during the initial 15 min of incubation. Thereafter the production rate from the L-isomer accelerated while that from the D-isomer remained constant. The accelerated rate of ammonia production from L-glutamine was dependent upon tissue swelling since prevention of swelling reduced the production rate. Swelling activates the mitochondrial glutaminase I pathway as evidenced by the rise in ammonia produced per glutamine utilized ratio as well as by the accelerated rate of CO2 production derived from the oxidative disposal of glutamin's carbon skeleton. Cortical slice swelling activates the mitochondrial pathway in a manner not unlike that seen in vivo during chronic acidosis and may reflect increased permeability to glutamine. Acidotic rat kidneys are not swollen in vivo while cortical slices initially produce 4-fold more ammonia than do non-acidotic slices. After 15 min, this 4-fold difference in total ammonia production drops to only a 2-fold difference due to the swelling-induced activation of the mitochondrial pathway. Consequently, slice swelling obliterates the important fact that ammonia production by the mitochondrial pathway is 15-fold greater in acidotic than in non-acidotic kidneys.