FUNCTIONAL-CHANGES IN NONADRENERGIC, NONCHOLINERGIC INHIBITORY NEURONS IN ILEAL CIRCULAR SMOOTH-MUSCLE AFTER SMALL-BOWEL TRANSPLANTATION INRATS

This experiment was designed to determine mechanisms of change in nona drenergic, noncholinergic (NANC) inhibitory neurons in the ileum after small bowel transplantation (SBT) in the rat and whether nitric oxide (NO) serves as an important NANC inhibitory neurotransmitter in the r at ileum. Eight groups of rats (N greater than or equal to 8 rats/grou p) were studied: neurally intact unoperated controls; rats one week af ter anesthesia and sham celiotomy; and separate groups one and eight w eeks after either 40 min of cold ischemia of the jejunoileum, combined jejunal and ileal intestinal transection/reanastomosis, or orthotopic SET of the entire jejunoileum. Contractile activity was evaluated in full-thickness ileal circular muscle strips under isometric conditions . Spontaneous activity did not differ among groups. In all groups, exo genous NO, N-G-monomethyl-L-arginine (L-NMMA, an NO synthase inhibitor ), and methylene blue (soluble guanylate cyclase inhibitor) had no eff ect on spontaneous activity, while 8-bromocyclic guanosine monophospha te (8Br-cGMP) inhibited contractile activity in all groups. Low freque ncy (2-10 Hz) electrical field stimulation (EFS) inhibited contractile activity only in control and SET groups; L-NMMA and methylene blue di d not alter the response to EFS in any group. These results suggest th at each aspect of the SET procedure, ischemia/reperfusion injury, disr uption of enteric neural continuity by intestinal transection, and ext rinsic denervation, alter function of enteric ileal inhibitory neurons separately early (one week) after operation. NO, a known inhibitory n eurotransmitter in other gut regions, does not affect ileal circular m uscle in neurally intact tissue nor mediate functional changes in inhi bitory nerve function nor smooth muscle contractility after SET.