Role of extrinsic innervation in modulating nitrergic transmission in the canine ileocolonic region.
The human colon can dilate, often to life-threatening proportions. Our aim was to explore nitrergic mechanisms underlying colonic dilation in conscious dogs with enterically isolated ileocolonic loops either extrinsically innervated (n = 4) or extrinsically denervated (n = 4). We recorded phasic pressures in ileum and ileocolonic sphincter (ICS), colonic tone, compliance, and relaxation during ileal distension. By NADPH-diaphorase histochemistry, we assessed effects of extrinsic denervation and enteric isolation on nitrergic fibers. Extrinsic denervation increased phasic pressures in ileum, ICS, and colon and abolished ICS and colonic relaxation in response to ileal distension. The nitric oxide synthase (NOS) inhibitor N(omega)-nitro-L-arginine (L-NNA) increased phasic pressures at all sites and ICS tone but did not abolish colonic relaxation during ileal distension in innervated loops. L-NNA reduced compliance and induced colonic high-amplitude propagated contractions in denervated loops. The NOS substrate donor L-arginine reversed effects of L-NNA. The number of NADPH-diaphorase fibers increased in both enterically isolated preparations. Nonnitrergic extrinsic nerve pathways mediate reflex colonic relaxation during ileal distension. Enteric isolation augments the number of NOS fibers, an effect not modified by extrinsic denervation.
Leelakusolvong
Somchai
S
Division of Gastroenterology and Hepatology, Gastroenterology Research Unit and Enteric Neurosciences Program, Mayo Clinic, Rochester, Minnesota 55905, USA.
Sarr
Michael G
MG
Miller
Steven M
SM
Phillips
Sidney F
SF
Bharucha
Adil E
AE
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002404:Catheterization; D003106:Colon / Q000187:drug effects / Q000294:innervation*; D003714:Denervation; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology; D007082:Ileum / Q000187:drug effects / Q000294:innervation*; D009129:Muscle Tonus / Q000187:drug effects; D009130:Muscle, Smooth / Q000502:physiology; D009252:NADPH Dehydrogenase / Q000378:metabolism; D009424:Nervous System Physiological Phenomena; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine / Q000494:pharmacology; D009435:Synaptic Transmission / Q000502:physiology*
D004791:Enzyme Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D009252:NADPH Dehydrogenase