Adenosine production in the ischemic kidney

Experiments were conducted to determine tissue, blood, and urine levels of adenosine produced by the ischemic kidney under conditions of renal artery occlusion, and the site(s) of production and release of adenosine by the kidney. Concentrations of adenosine, inosine, and hypoxanthine in the dog urine were found to increase after 2 minutes of renal artery occlusion as were concentrations fo these metabolites in renal tissue after 10 minutes of renal artery occlusion. Renal venous plasma levels of inosine and hypoxanthine also were elevated after 3 minutes of arterial occlusion. In modified stop-flow experiments, adenosine appeared in the urine in a peak that corresponded most closely with proximal tubule fluid. 5'-Nucleotidase, the enzyme which catalyzes the dephosphorylation of 5'-AMP or 5'-IMP to adenosine or inosine, respectively, was found to be located primarily on the external membranes and mitochondria of proximal tubule cells, but not in distal tubule or collecting duct cells. Since adenosine has been demonstrated to elicit renal vasoconstriction and is produced by the ischemic kidney, it is suggested that adenosine may be involved in the mediation of postocclusion renal ischemia.