Effects of extrinsic denervation on innervation with VIP and substance P in circular muscle of rat jejunum1

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 ≥ 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‐Phe⁶,Leu¹⁷]‐VIP) did not prevent the inhibition by exogenous VIP in any group, while the Sub P antagonist ([d ‐Pro²,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.