TY - JOUR
T1 - Small Bowel Transplantation Induces Adrenergic Hypersensitivity in Ileal Longitudinal Smooth Muscle in Rats
AU - Ohtani, Noriya
AU - Balsiger, Bruno M.
AU - Anding, William J.
AU - Duenes, Judith A.
AU - Sarr, Michael G.
N1 - Funding Information:
Relaxation and/or inhibition of contractile activity of the gut is mediated in part by a class of nerves within the gut wall referred to as nonadrenergic, non-cholinergic (NANC) nerves because their inhibitory neurotransmitter is neither acetylcholine nor norepinephrine. 3,4 Nitric oxide (NO) appears to be one of the primary mediators of smooth muscle relaxation induced by NANC nerves. 5 NO also regulates or modulates many other gastrointestinal functions including motility patterns and secretion. 6-s Morphologic studies have demonstrated an increase in ni-trergic nerves in guinea pig ileum after extrinsic den- Supported in part by grant DK 39337 from the National Institutes of Health, the Mayo Foundation, and the First Deparunent of Surgery, Tohoku University, Sendai, Japan. Parts of this work were presented at the Fortieth Annual Meeting of The Societyf or Surgery of the Alimentary Tract, May 16-19, 1999, and the annual meeting of the American Gastroenterological Association, May 16-19, 1999, Orlando, Fla., and published as two abstracts in Gastroenterology1 16:A139 and A1075, 1999. Correspondence: Michael G. Sarr, M.D., Professor of Surgery, Gastroenterology Research Unit, Mayo Clinic, 200 First Street SW, Rochester, MN 55905.
PY - 2000
Y1 - 2000
N2 - Our aim was to determine the effects of small bowel transplantation on contractility of longitudinal muscle in the rat ileum. Full-thickness longitudinal muscle strips from four groups of rats (naive controls, sham-operated controls, and 1 week and 8 weeks after syngeneic orthotopic small bowel transplantation) were studied in vitro. Neither baseline contractility nor response to neural blockade (tetrodotoxin) or adrenergic/cholinergic blockade differed among the groups. Although the dose response to the cholinergic agonist bethanechol and to nitric oxide did not differ among groups, the ED50 (negative log of concentration giving half-maximal effect) for the adrenergic agonist norepinephrine was increased 1 week and 8 weeks after transplantation, indicating a hypersensitivity response not blocked by tetrodotoxin. Nonadrenergic, noncholinergic inhibitory responses to electrical field stimulation were of greater amplitude and occurred at lesser frequencies (≤5 Hz) 1 week after small bowel transplantation, but returned to control values 8 weeks postoperatively. These inhibitory responses were blocked by the nitric oxide synthase inhibitor L-NMMA but not by methylene blue, a nonspecific inhibitor of guanylate cyclase. Small bowel transplantation induces a persistent adrenergic denervation hypersensitivity at the muscle and appears to upregulate, at least transiently, other inhibitory mechanisms mediated by neural release of nitric oxide. Small bowel transplantation does not alter muscle response to cholinergic pathways. These alterations in smooth muscle contractility may affect gut function early after clinical small bowel transplantation.
AB - Our aim was to determine the effects of small bowel transplantation on contractility of longitudinal muscle in the rat ileum. Full-thickness longitudinal muscle strips from four groups of rats (naive controls, sham-operated controls, and 1 week and 8 weeks after syngeneic orthotopic small bowel transplantation) were studied in vitro. Neither baseline contractility nor response to neural blockade (tetrodotoxin) or adrenergic/cholinergic blockade differed among the groups. Although the dose response to the cholinergic agonist bethanechol and to nitric oxide did not differ among groups, the ED50 (negative log of concentration giving half-maximal effect) for the adrenergic agonist norepinephrine was increased 1 week and 8 weeks after transplantation, indicating a hypersensitivity response not blocked by tetrodotoxin. Nonadrenergic, noncholinergic inhibitory responses to electrical field stimulation were of greater amplitude and occurred at lesser frequencies (≤5 Hz) 1 week after small bowel transplantation, but returned to control values 8 weeks postoperatively. These inhibitory responses were blocked by the nitric oxide synthase inhibitor L-NMMA but not by methylene blue, a nonspecific inhibitor of guanylate cyclase. Small bowel transplantation induces a persistent adrenergic denervation hypersensitivity at the muscle and appears to upregulate, at least transiently, other inhibitory mechanisms mediated by neural release of nitric oxide. Small bowel transplantation does not alter muscle response to cholinergic pathways. These alterations in smooth muscle contractility may affect gut function early after clinical small bowel transplantation.
KW - Adrenergic nerves
KW - Adrenergic receptors
KW - Cholinergic receptors
KW - Denervation hypersensitivity
KW - Small bowel transplantation
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U2 - 10.1016/s1091-255x(00)80036-0
DO - 10.1016/s1091-255x(00)80036-0
M3 - Article
C2 - 10631366
AN - SCOPUS:0033627728
SN - 1091-255X
VL - 4
SP - 77
EP - 85
JO - Journal of Gastrointestinal Surgery
JF - Journal of Gastrointestinal Surgery
IS - 1
ER -