Redistribution of cellular energy following renal ischemia.
In order to elucidate the pattern of redistribution of cellular energy and the restoration of basic cellular metabolism following an ischemic renal insult, suspensions enriched in proximal tubule segments were studied after 45 min of bilateral artery occlusion and 15 min and 2 h of reflow from rats given either normal saline (control), ATP-MgCl2 (which enhances postischemic recovery of ATP), or alpha, beta-methyl adenosine diphosphate (AMPCP), which inhibits nucleotide degradation during ischemia. In non-ischemic control animals, approximately half of the energy is distributed to functional pump activity and half directed for non-transport purposes. When cellular ATP is reduced to 56% of control values, functional pump activity is significantly reduced to 61% of control, while energy delegated for non-transport purposes is decreased by a significantly smaller increment to only 78% of control at 15 min of reflow. In animals given ATP-MgCl2, the cellular and metabolic profile at 15 min of reflow was no different from ischemic control animals with cellular ATP levels similar at 58%. However, by 2 h, cellular ATP levels had increased significantly to 74%, and this was associated with a redistribution of cellular energy to functional pump activity (119% of control) with little change in non-transport function (76%). In animals treated with AMPCP, the cellular ATP levels were 74% of controls, similar to ATP-MgCl2-treated rats after 2 h of reflow. Despite the differences in reflow interval, the distribution of cellular energy was similar (functional pump activity 120% and non-transport activity 79%). By 2 h, cellular ATP was at 95% and both functional pump activity and non-transport activity were 100%.(ABSTRACT TRUNCATED AT 250 WORDS)
Gaudio
K M
KM
Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06510.
Thulin
G
G
Ardito
T
T
Kashgarian
M
M
Siegel
N J
NJ
D058186:Acute Kidney Injury / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects; D066298:In Vitro Techniques; D007511:Ischemia / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply* / Q000737:chemistry / Q000187:drug effects; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism; D008854:Microscopy, Electron; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
C523965:alpha,beta-methyleneadenosine 5'-diphosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate