Physiologic Studies on Nitric Oxide in Rat Small Bowel Isografts

The enteric nervous system (ENS), especially the nonadrenergic noncholinergic (NANC) inhibitory nerves, is an important factor in intestinal peristalsis. Recently, it was established that nitric oxide (NO) is released after stimulation of NANC inhibitory nerves. Inhibitory nerves such as NANC inhibitory nerves in the ENS are more easily damaged than excitatory nerves by reperfusion or ischemic injuries during small bowel transplantation (SBT). To evaluate the effects of reperfusion and ischemic injuries to the ENS in the transplanted small bowel, we examined the ENS responses, including the effects of NO in the isografted rat jejunum, using the nontransplanted jejunum as a control. To avoid potentially confounding immune phenomena, we used syngeneic Lewis (LEW) rats. Orthotopic entire SBT with portocaval drainage was performed from LEW rats to LEW rats. Isografted muscle strips were obtained from 8 LEW rats 130 days after SBT (n = 24). As controls, normal muscle strips of the jejunum were obtained from 20 nontransplanted LEW rats (n = 60). A mechanograph was used to evaluate in vitro jejunal responses to electrical field stimulation of the adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers, Ng-nitro-l-arginine (L-NNA), and l-arginine. The results indicated that excitatory nerves, especially NANC excitatory nerves, were more dominant in the isografted jejunum than in the normal jejunum (p < 0.01). NANC inhibitory nerves were found to act on the normal jejunum and to a lesser extent on the isografted jejunum (p < 0.05). NO mediates the relaxation reaction of NANC inhibitory nerves in the normal jejunum and to a lesser extent in the isografted jejunum. These results indicated that the intrinsic intestinal innervation contains excitatory and inhibitory nerves and that the former, especially NANC excitatory nerves, are more dominant in the isografted jejunum than in the normal jejunum. In addition, reduction of the action of NANC inhibitory nerves such as that by NO may be largely related to impaired motility in the isografted jejunum. Thus over a long period of time (more than 130 days after SBT) transplanted small bowel dysmotility may be influenced by reperfusion or ischemic injury to the ENS (especially NANC inhibitory nerves) via NO in the transplanted jejunum after syngeneic SBT.