Metabolic and functional consequences of inhibiting adenosine deaminase during renal ischemia in rats.
The concentrations of renal ATP have been measured by 31P-nuclear magnetic resonance (NMR) before, during, and after bilateral renal artery occlusion. Using in vivo NMR, the initial postischemic recovery of ATP increased with the magnitude of the residual nucleotide pool at the end of ischemia. ATP levels after 120 min of reflow correlated with functional recovery at 24 h. In the present study the effect of blocking the degradation of ATP during ischemia upon the postischemic restoration of ATP was investigated. Inhibition of adenosine deaminase by 80% with the tight-binding inhibitor 2'-deoxycoformycin led to a 20% increase in the residual adenine nucleotide pool. This increased the ATP initial recovery after 45 min of ischemia from 52% (in controls) to 62% (in the treated animals), as compared to the basal levels. The inhibition also caused an accelerated postischemic restoration of cellular ATP so that at 120 min it was 83% in treated rats vs. 63% in untreated animals. There was a corresponding improvement in the functional recovery from the insult (increase of 33% in inulin clearance 24 h after the injury). Inhibition of adenosine deaminase during ischemia results in a injury similar to that seen after a shorter period of insult.
Stromski
M E
ME
Department of Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06510.
van Waarde
A
A
Avison
M J
MJ
Thulin
G
G
Gaudio
K M
KM
Kashgarian
M
M
Shulman
R G
RG
Siegel
N J
NJ
D058892:Adenosine Deaminase Inhibitors; D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D003070:Coformycin / Q000031:analogs & derivatives / Q000494:pharmacology; D007444:Inulin / Q000493:pharmacokinetics; D007511:Ischemia; D007668:Kidney / Q000098:blood supply*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009700:Nucleoside Deaminases / Q000037:antagonists & inhibitors*; D015649:Pentostatin; D051381:Rats; D011919:Rats, Inbred Strains
D058892:Adenosine Deaminase Inhibitors; D003070:Coformycin; D015649:Pentostatin; D000255:Adenosine Triphosphate; D007444:Inulin; D009700:Nucleoside Deaminases