Nucleotides modulate renal ischaemia-reperfusion injury by different effects on nitric oxide and superoxide

1. The present study investigated the effects of kidney ischaemia duration on nitric oxide (NO) and superoxide (O2-) generation at reperfusion and the role of xanthine and adenosine as mediators of NO/O2- generation. 2. The effect of the duration of ischaemia on renal nucleotide levels was studied in two ischaemic groups (10 and 30 min). The role of adenosine and xanthine was studied in ischaemic-reperfused groups (subjected to 10 and 30 min ischaemia and 60 min reperfusion). 3. Tissue levels of adenosine decreased significantly after 30 min ischaemia, whereas xanthine/hypoxanthine levels increased concomitantly with renal dysfunction and histological damage. 4. Nitric oxide production increased significantly after 10 min ischaemia and 60 min reperfusion, whereas lipoperoxidation increased significantly after 30 min ischaemia and 60 min reperfusion. The administration of theophylline (40 mg/kg, i.p.) reversed the early increase in NO production. 5. Xanthine supplementation decreased renal function and increased lipoperoxidation. 6. In conclusion, NO/O2- production and the subsequent renal injury/dysfunction may be modified by changes in the adenosine and xanthine levels of the injured kidney, although the present data show a significant in vivo role only for xanthine.