Attenuation of renal ischemia-reperfusion injury by postconditioning involves adenosine receptor and protein kinase C...

Significant organ injury occurs after transplantation and reflow (i.e., reperfusion injury). Postconditioning (PoC), consisting of alternating periods of reperfusion and re-occlusion at onset of reperfusion, attenuates reperfusion injury in organs including heart and brain. We tested whether PoC attenuates renal ischemia-reperfusion (I/R) injury in the kidney by activating adenosine receptors (AR) and protein kinase C (PKC). The single kidney rat I/R model was used. Groups: (1) sham: time-matched surgical protocol only. In all others, the left renal artery (RA) was occluded for 45 min and reperfused for 24 h. (2) CONTROL: I/R with no intervention at R. All antagonists were administered 5 min before reperfusion. (3) PoC: I/R + four cycles of 45 s of R and 45 s of re-occlusion before full R. (4) PoC + ARi: PoC plus the AR antagonist 8-rho-(sulfophenyl) theophylline (8-SPT). (5) PoC + PKCi: PoC plus the PKC antagonist chelerythrine (Che). In shams, plasma blood urea nitrogen (BUN mg/dl) at 24 h averaged 23.2 +/- 5.3 and creatinine (Cr mg/dl) averaged 1.28 +/- 0.2. PoC reduced BUN (87.2 +/- 10 in CONTROL vs. 38.8 +/- 9, P = 0.001) and Cr (4.2 +/- 0.6 in CONTROL vs. 1.5 +/- 0.2, P < 0.001). 8-SPT and Che reversed renal protection indices after PoC. I/R increased apoptosis, which was reduced by PoC, which was reversed by 8-SPT and Che. Postconditioning attenuates renal I/R injury by adenosine receptor activation and PKC signaling.