[show abstract][hide abstract] ABSTRACT: This study was designed to evaluate the role of nitric oxide (NO) in ischemia-reperfusion injury (IRI) and acute rejection (AR) in rat intestinal transplantation, using administration of the NO inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME).
Rats that underwent orthotopic allogeneic intestinal transplantation were assigned to 2 groups. In the normal allograft group (Wistar to Sprague-Dawley rats), L-NAME 0 mg/kg/d (group 1-1), 4 mg/kg/d (group 1-2), 8 mg/kg/d (group 1-3), or 12 mg/kg/d (group 1-4) was injected intraperitoneally. In the high responder allograft group (Dark Agouti to Lewis rats), L-NAME 0 mg/kg/d (group 2-1) or 8 mg/kg/d (group 2-2) was injected intraperitoneally. Survival times were observed and maltose absorption tests performed as well as light microscopic examination of the grafts.
The mean survival time of group 1-3 was significantly prolonged compared with group 1-1 (P < .01). In group 2, the survival time of group 2-2 was significantly prolonged compared with group 2-1 (P < .01). Histological changes showed IRI was attenuated in group 1-2 compared with group 1-1, whereas it was aggravated in groups 1-3 and 1-4. Treatment with L-NAME (8 mg/kg/d) attenuated the graft damage of AR in groups 1 and 2. Maltose absorption tests showed that inhibition of NO impaired maltose absorption.
This study suggested that NO plays a dual role as both a cytotoxic and a cytoprotective factor in IRI, and may serve as a kind of cytotoxic medium in AR in rat intestinal allotransplantation.
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