Renal metabolism during normoxia, hypoxia, and ischemic injury.
The reversible period of hypoxia and ischemia is a consequence of the function of numerous regulatory mechanisms which convert cells to a quiescent state. Thus, early changes in metabolism reflect regulatory events rather than pathological events. O2-dependent enzymes (oxidases and oxygenases) are the primary sensors for physiological responses to hypoxia, and failure of their functions are ultimately responsible for hypoxic and ischemic cell injury. At least 30 of these enzymes are known to occur in kidney, but only cytochrome oxidase has been extensively studied with regard to the above processes. Heterogeneity of subcellular oxygenation occurs as a result of the existence of clusters of mitochondria in the basolateral regions of proximal and distal tubule cells. This creates regions with very high O2 consumption rates, and results in diffusion limitations in O2 supply. Finally, dramatic progress has been made in protecting against ischemic injury through use of nonpermeant solutes to reduce cell swelling, addition of ATP-MgCl2 to stimulate recovery of cellular adenylates upon reoxygenation, use of a Ca2+ uptake blocker to prevent cellular loading of Ca2+, and addition of compounds to inhibit superoxide and H2O2 production or scavenge reactive O2 species. While the mechanistic details and complete description of metabolic effects are not yet available, the ability to alter cellular metabolism and delay or prevent irreversible injury marks a very important advance in renal physiology.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002463:Cell Membrane Permeability; D004734:Energy Metabolism; D004921:Erythropoietin / Q000378:metabolism; D005609:Free Radicals; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D007511:Ischemia / Q000188:drug therapy / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010105:Oxygenases / Q000378:metabolism; D051381:Rats
D005609:Free Radicals; D004921:Erythropoietin; D000255:Adenosine Triphosphate; D010088:Oxidoreductases; D010105:Oxygenases; D010100:Oxygen; D002118:Calcium