title: Attenuation of renal ischemia-reperfusion injury by postconditioning involves adenosine receptor and protein kinase C activation.
abstract: 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.
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, Emory University School of Medicine and Carlyle Fraser Heart Center Cardiothoracic Research Laboratory, Emory Crawford Long Hospital, Atlanta, GA 30308-2225, USA.
authors.forename: Shady M
authors.initials: SM
authors.lastname: Eldaif
authors.forename: Jeremiah A
authors.initials: JA
authors.lastname: Deneve
authors.forename: Ning-Ping
authors.initials: NP
authors.lastname: Wang
authors.forename: Rong
authors.initials: R
authors.lastname: Jiang
authors.forename: Mario
authors.initials: M
authors.lastname: Mosunjac
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Mutrie
authors.forename: Robert A
authors.initials: RA
authors.lastname: Guyton
authors.forename: Zhi-Qing
authors.initials: ZQ
authors.lastname: Zhao
authors.forename: Jakob
authors.initials: J
authors.lastname: Vinten-Johansen
mesh_terms: D000818:Animals; D017209:Apoptosis; D053119:Benzophenanthridines / Q000494:pharmacology; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D004789:Enzyme Activation; D007668:Kidney / Q000098:blood supply* / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000473:pathology / Q000502:physiology; D008297:Male; D011184:Postoperative Period; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D015398:Signal Transduction; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D019172:Transplantation Conditioning / Q000379:methods*
chemical_list: D053119:Benzophenanthridines; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; C031433:8-(4-sulfophenyl)theophylline; D003404:Creatinine; D013806:Theophylline; C016299:chelerythrine; D011493:Protein Kinase C