Regional responses within the kidney to ischemia: assessment of adenine nucleotide and catabolite profiles.
Renal cortex (C) has predominantly aerobic metabolism, whereas inner medulla (IM) has both aerobic and anaerobic capacities. This study was undertaken (1) to assess how well rat IM anaerobic metabolism maintains this region's ATP content during ischemia; and (2) to determine whether regional variations in adenylate pool/catabolite responses to ischemia exist, obscuring interpretation of cellular energetics in rat studies of acute renal failure (ARF). Adenine nucleotides/catabolites were measured in rat C, IM and outer medulla (OM) after 15 and 45 min of ischemia. After 15 min, all regions showed profound ATP depletion, although the IM maintained slightly higher (by 0.23 mumol/g) absolute ATP levels than C/OM tissues (normal ATP value = 8.7 mumol/g). By 45 min, significant differences in regional ATP levels did not exist. Striking regional catabolite differences were apparent at both 15 and 45 min. Most prominent were: (1) intrarenal purine base/inosine gradients, levels falling approx. 22-50% from C to IM; and (2) preferential OM AMP/IMP/adenosine accumulation. To assess whether more homogeneous results might be found in rabbit kidney, possibly making this animal preferable to rats for studies of renal ischemia, rabbit C, OM and IM adenylate pools were analyzed after 15 min of ischemia. C vs. IM ATP differences were greater (approx. 1.3 mumol/g) and large catabolite concentration differences were still apparent.


CONCLUSIONS
(1) anaerobic mechanisms support IM ATP levels during ischemia but, in terms of normal concentrations, the impact is small, particularly in the rat; and (2) marked regional differences in adenylate catabolite levels exist within ischemic kidneys. These need to be recognized when analyzing adenylate pool responses in ischemic ARF.
Zager
R A
RA
Department of Medicine, University of Washington, Seattle.
Gmur
D J
DJ
Bredl
C R
CR
Eng
M J
MJ
Fisher
L
L
D058186:Acute Kidney Injury / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D005260:Female; D007511:Ischemia / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D007672:Kidney Cortex / Q000098:blood supply; D007679:Kidney Medulla / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains
D010710:Phosphates; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate