The enhancement of cellular cAMP with olprinone protects autotransplanted rat kidney against cold ischemia-reperfusion injury.
The administration of a cyclic nucleotide analog improves cold ischemia/reperfusion injury in several organs. The type 3 phosphodiesterase inhibitor olprinone is a potent stimulus that enhances cellular cAMP levels. The present study was performed to investigate the protective effects of enhanced intracellular cAMP levels by olprinone in rat orthotopic kidney transplantation. Autotransplantation and immediate contralateral nephrectomy were performed in Lewis rats after 18 hours of graft storage at 4 degrees C in University of Wisconsin (UW) solution with or without 25 microg/mL olprinone hydrochloride. At 2 hours after reperfusion, serum and urinary biochemical indicators of renal dysfunction and injury were measured: serum creatinine, fractional excretion of Na+ and urinary N-acetyl-D-glucosaminidase. Additionally, intracellular cAMP in kidney tissues was measured by a radioimmunology method. Compared to the only UW solution group, olprinone hydrochloride significantly reduced the increased in serum creatinine, FENa and NAG caused by renal ischemia/reperfusion injury, after 2 hours of reperfusion. The content of cAMP at the endpoint of 18 hours cold preservation was significantly greater in the UW plus olprinone hydrochloride group than that in the UW group. Two hours after reperfusion, the content of cAMP in the UW plus olprinone hydrochloride group was still significantly higher than that in the UW group without containing olprinone hydrochloride. These results support a beneficial effect of olprinone against cold ischemia and reperfusion injury via an increased intracellular cAMP levels.
Zhang
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Department of Surgical Oncology, First Hospital of Xi'an Jiaotong University, Xi'an, P.R. China. sage2001china@hotmail.com
Ma
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D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000502:physiology*; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology; D008297:Male; D023421:Models, Animal; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011728:Pyridones / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000517:prevention & control*; D014182:Transplantation, Autologous
D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D011728:Pyridones; C059498:olprinone; D000242:Cyclic AMP