Effect of chronic, extrinsic denervation on functional NANC innervation with vasoactive intestinal polypeptide and substance P in longitudinal muscle of rat jejunum.

Abstract Intestinal denervation contributes to enteric motor dysfunction after intestinal transplantation [small bowel transplantation (SBT)]. Our aim was to determine long‐term effects of extrinsic denervation on functional non‐adrenergic, non‐cholinergic innervation with vasoactive intestinal polypeptide (VIP) and substance P. Contractile activity of jejunal longitudinal muscle from six age‐matched, naïve control rats (NC) and eight rats 1 year after syngeneic SBT were studied in tissue chambers. Spontaneous contractile activity did not differ between groups. Exogenous VIP inhibited contractile activity dose‐dependently in both groups, greater in NC than in SBT. The VIP antagonist ([d ‐p‐Cl‐Phe⁶,Leu¹⁷]‐VIP) and the nitric oxide synthase inhibitor l ‐N^G‐nitro arginine prevented inhibition by exogenous VIP and electrical field stimulation (EFS) in both groups. Exogenous substance P increased contractile activity dose‐dependently, greater in NC than in SBT. The substance P antagonist ([d ‐Pro²,d ‐Trp^7,9]‐substance P) inhibited effects of exogenous substance P and increased the EFS‐induced inhibitory response. Immunohistofluorescence showed staining for tyrosine hydroxylase in the jejunoileum 1 year after SBT suggesting sympathetic reinnervation. In rat jejunal longitudinal muscle after chronic denervation, response to exogenous VIP and substance P is decreased, while endogenous release of both neurotransmitters is preserved. These alterations in excitatory and inhibitory pathways occur despite extrinsic reinnervation and might contribute to enteric motor dysfunction after SBT.