Renal interstitial adenosine metabolism during ischemia in dogs

The present study was conducted to determine the metabolism of renal inters titial adenosine under resting conditions and during ischemia. By using a m icrodialysis method with HPLC-fluorometric analysis, renal interstitial con centrations of adenosine, inosine, and hypoxanthine were assessed in pentob arbital-anesthetized dogs. Average basal renal interstitial concentrations of adenosine, inosine, and hypoxanthine were 0.18 +/- 0.04, 0.31 +/- 0.05, and 0.35 +/- 0.05 mu mol/l, respectively. Local inhibition of adenosine kin ase with iodotubercidin (10 mu mol/l in perfusate) or inhibition of adenosi ne deaminase with erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA; 100 mu mol/l in perfusate) did not change adenosine concentrations in the nonischemic ki dneys (0.18 +/- 0.04 and 0.24 +/- 0.05 mu mol/l, respectively). On the othe r hand, treatment with iodotubercidin+EHNA significantly increased adenosin e concentration (0.52 +/- 0.07 mu mol/l) with significant decreases in inos ine and hypoxanthine levels (0.13 +/- 0.03 and 0.19 +/- 0.04 mu mol/l, resp ectively). During 30 min of ischemia, adenosine, inosine, and hypoxanthine were significantly increased to 0.76 +/- 0.29, 2.14 +/- 0.45, and 21.8 +/- 4.7 mu mol/l, respectively. The treatment with iodotubercidin did not alter ischemia-induced increase in adenosine (0.84 +/- 0.18 mu mol/l); however, EHNA alone markedly enhanced adenosine accumulation (13.54 +/- 2.16 mu mol/ l), the value of which was not augmented by an addition of iodotubercidin ( 15.80 +/- 1.24 mu mol/l). In contrast, ischemia-induced increases in inosin e and hypoxanthine were inversely diminished by the treatment with iodotube rcidin+EHNA (0.90 +/- 0.20 and 9.86 +/- 1.96 mu mol/l, respectively). These results suggest that both adenosine kinase and adenosine deaminase contrib ute to the metabolism of renal interstitial adenosine under resting conditi ons, whereas adenosine produced during ischemia is mainly metabolized by ad enosine deaminase and the rephosphorylation of adenosine by adenosine kinas e is small.