Generation of nitric oxide as a rejection marker in rat pancreas transplantation

In clinical pancreas transplantation, no reliable marker for the early diagnosis of acute rejection has been reported. This is one reason why the graft survival rate of pancreas transplantation alone is much lower than that of other organs, such as hearts, livers, and kidneys. We designed an experiment to investigate acute rejection of pancreas allografts in hyperglycemic rats by measurement of blood glucose levels and nitric oxide (NO) products (nitrite plus nitrate, and nitrosyl hemoglobin). As recipients, Lewis rats were rendered hyperglycemic by intravenous injection of streptozotocin before transplantation. F344 rats were used as donors of pancreas allografts. Lewis rats were also used as donors of syngeneic pancreas grafts. After transplantation, the blood glucose level returned to a normal level and rejection was defined as the recurrence of hyperglycemia. The mean survival time of pancreas allografts was 14 +/- 0.7 days. The plasma level of nitrite plus nitrate in allografted rats peaked on postoperative day 7. Electron spin resonance spectra of NO bound to hemoglobin were detected in the blood from allografted rats with a peak on postoperative day 7, whereas NO bound to hemoglobin was not detected in the blood from recipients of syngeneic grafts at any sampling time. The results show that NO was synthesized in the earlier period than the elevation of the blood glucose level during rejection after pancreas transplantation in rats.