Small bowel transplantation induces adrenergic hypersensitivity in ileal longitudinal smooth muscle in rats

Our aim was to determine the effects of small bowel transplantation on cont ractility of longitudinal muscle in the rat ileum. Full-thickness longitudi nal muscle strips from four groups of rats (naive controls, sham-operated c ontrols, and 1 week and 8 weeks after syngeneic orthotopic small bowel tran splantation) were studied in vitro. Neither baseline contractility nor resp onse to neural blockade (tetrodotoxin) or adrenergic/cholinergic blockade d iffered among the groups. Although the dose response to the cholinergic ago nist bethanechol and to nitric oxide did not differ among groups, the ED50 (negative log of concentration giving half-maximal effect) for the adrenerg ic agonist norepinephrine was increased 1 week and 8 weeks after transplant ation, indicating a hypersensitivity response not blocked by tetrodotoxin. Nonadrenergic, noncholinergic inhibitory responses to electrical field stim ulation were of greater amplitude and occurred at lesser frequencies (less than or equal to 5 Hz) 1 week after small bowel transplantation, but return ed to control values 8 weeks postoperatively. These inhibitory responses we re blocked by the nitric oxide synthase inhibitor L-NMMA but not by methyle ne blue, a nonspecific inhibitor of guanylate cyclase. Small bowel transpla ntation induces a persistent adrenergic denervation hypersensitivity at the muscle and appears to upregulate, at least transiently, other inhibitory m echanisms mediated by neural release of nitric oxide. Small bowel transplan tation does not alter muscle response to cholinergic pathways. These altera tions in smooth muscle contractility may affect gut function early after cl inical small bowel transplantation.