Kidney outer medulla mitochondria are more efficient compared with cortex mitochondria as a strategy to sustain ATP production in a suboptimal environment

The kidneys receive ~25% of cardiac output, which is a prerequisite to maintain sufficient glomerular filtration rate. However, both intrarenal regional renal blood flow and tissue oxygen levels are heterogeneous with decreasing levels in the inner part of the medulla. These differences, in combination with the heterogeneous metabolic activity of the different nephron segment located in the different parts of the kidney, may constitute a functional problem when challenged. The proximal tubule and the medullary thick ascending limb of Henle are considered to have the highest metabolic rate, which is related to the high mitochondria content needed to sustain sufficient ATP production from oxidative phosphorylation to support high electrolyte transport activity in these nephron segments. Interestingly, the cells located in kidney medulla function at the verge of hypoxia, and the mitochondria may have adapted to the surrounding environment. However, little is known about intrarenal differences in mitochondria function. We therefore investigated functional differences between mitochondria isolated from kidney cortex and medulla of healthy normoglycemic rats by using high-resolution respirometry. The results demonstrate that medullary mitochondria had a higher degree of coupling, are more efficient, and have higher oxygen affinity, which would make them more suitable to function in an environment with limited oxygen supply. Furthermore, these results support the hypothesis that mitochondria of medullary cells have adapted to the normal hypoxic in vivo situation as a strategy of sustaining ATP production in a suboptimal environment.

Renal cortical and medullary blood flow responses to altered NO availability in humans

The objective of this study was to quantify regional renal blood flow in humans. In nine young volunteers on a controlled diet, the lower abdomen was CT-scanned, and regional renal blood flow was determined by positron emission tomography (PET) scanning using H215O as tracer. Measurements were performed at baseline, during constant intravenous infusion of nitric oxide (NO) donor glyceryl nitrate and after intravenous injection of NO synthase inhibitor Nω-monomethyl-l-arginine (l-NMMA). Using the CT image, the kidney pole areas were delineated as volumes of interest (VOI). In the data analysis, tissue layers with a thickness of one voxel were eliminated stepwise from the external surface of the VOI (voxel peeling), and the blood flow subsequently was determined in each new, reduced VOI. Blood flow in the shrinking VOIs decreased as the number of cycles of voxel peeling increased. After 4–5 cycles, blood flow was not reduced further by additional voxel peeling. This volume-insensitive flow was measured to be 2.30 ± 0.17 ml·g tissue−1·min−1 during the control period; it increased during infusion of glyceryl nitrate to 2.97 ± 0.18 ml·g tissue−1·min−1 ( P < 0.05) and decreased after l-NMMA injection to 1.57 ± 0.17 ml·g tissue−1·min−1 ( P < 0.05). Cortical blood flow was 4.67 ± 0.31 ml·g tissue−1·min−1 during control, unchanged by glyceryl nitrate, and decreased after l-NMMA [3.48 ± 0.23 ml·(g·min)−1, P < 0.05]. PET/CT scanning allows identification of a renal medullary region in which the measured blood flow is 1) low, 2) independent of reduction in the VOI, and 3) reactive to changes in systemic NO supply. The technique seems to provide indices of renal medullary blood flow in humans.