Protection of the kidney against ischemic injury by inhibition of 5'-nucleotidaseVan 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 journal › Article › Academic › peer-review
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.
|Journal||American Journal of Physiology|
|Issue number||2 Pt 2|
|Publication status||Published - Feb-1989|
- 5'-Nucleotidase, Adenosine Diphosphate, Animals, Hypoxanthine, Hypoxanthines, Ischemia, Kidney, Kinetics, Male, Nucleotidases, Rats, Rats, Inbred Strains, Renal Circulation