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Protection of the kidney against ischemic injury by inhibition of 5'-nucleotidase

Van Waarde, A., Stromski, M. E., Thulin, G., Gaudio, K. M., Kashgarian, M., Shulman, R. G. & Siegel, N. J., Feb-1989, In : American Journal of Physiology. 256, 2 Pt 2, p. F298-305

Research output: Contribution to journalArticleAcademicpeer-review

  • A Van Waarde
  • M E Stromski
  • G Thulin
  • K M Gaudio
  • M Kashgarian
  • R G Shulman
  • N J Siegel

We have evaluated the impact of inhibiting adenine nucleotide dephosphorylation on the metabolic and functional consequences of renal ischemia. Intramuscular injection of the ADP-analogue adenosine alpha, beta-methylene diphosphate (AMP-CP) achieved a 70% reduction in 5'-nucleotidase activity, as measured in crude extracts of rat kidney. AMPCP-treated animals had an increased residual nucleotide pool at the end of 45 min of ischemia compared with untreated rats. Assessment of renal ATP by 31P-nuclear magnetic resonance (31P-NMR) in vivo during reflow demonstrates the following: 1) higher rapid initial recovery of ATP (69.3 +/- 1.2 vs. 50.0 +/- 0.5% control value, P less than 0.005), 2) accelerated rate of ATP restoration (0.20 +/- 0.02 vs. 0.11 +/- 0.01% control/min, P less than 0.005), and 3) significantly enhanced renal ATP content after 120 min (93.6 +/- 2.0 vs. 63.1 +/- 0.7% control, P less than 0.005). Kidney function, as measured by the rate of inulin clearance 24 h after the insult, was also significantly improved in AMPCP-treated rats (725 +/- 50 vs. 313 +/- 28 microliters.min-1.100 g body wt-1). Thus inhibition of 5'-nucleotidase results in enhanced metabolic and functional recovery from a renal ischemic insult.

Original languageEnglish
Pages (from-to)F298-305
JournalAmerican Journal of Physiology
Volume256
Issue number2 Pt 2
Publication statusPublished - Feb-1989
Externally publishedYes

    Keywords

  • 5'-Nucleotidase, Adenosine Diphosphate, Animals, Hypoxanthine, Hypoxanthines, Ischemia, Kidney, Kinetics, Male, Nucleotidases, Rats, Rats, Inbred Strains, Renal Circulation

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