Abstract
Extrinsic denervation contributes to enteric motor dysfunction after small bowel transplantation (SBT). Our aim was to determine changes in nonadrenergic, noncholinergic innervation with vasoactive intestinal polypeptide (VIP) and substance P (Sub P) in rat jejunal circular muscle after SBT. Muscle strips were studied in tissue chambers from six groups of rats (n > or = 6 per group): naïve controls (NC), animals 1 week after anaesthesia/sham celiotomy (SC-1), and 1 and 8 weeks after jejunal and ileal transection/reanastomosis (TA-1, TA-8) and after syngeneic, orthotopic SBT (SBT-1, SBT-8). Response to exogenous VIP and Sub P and their endogenous release during electrical field stimulation (EFS) were studied. Exogenous VIP and Sub P caused a dose-dependent inhibition and stimulation of mechanical activity in all groups respectively (P < 0.05). The responses to VIP and Sub P were decreased (compared to NC) in all groups at 1 and 8 weeks postoperatively. The VIP antagonist ([D-p-Cl-Phe(6),Leu(17)]-VIP) did not prevent the inhibition by exogenous VIP in any group, while the Sub P antagonist ([D-Pro(2),D-Trp(7,9)]-Sub P) prevented the effect of exogenous Sub P in NC, TA-8 and SBT-8 (P < 0.05). Responses to exogenous VIP were unaffected by the nitric oxide synthase inhibitor l-N(G)-nitro arginine and precontraction of muscle strips with Sub P. Endogenous release of VIP and Sub P during EFS was preserved after SBT. In circular muscle of rat jejunum, changes in neuromuscular transmission with VIP and Sub P during the first 8 weeks after SBT are not mediated by extrinsic denervation.