MUCOSAL SENSORY TRANSDUCTION MECHANISMS TRIGGER DESCENDING NEURAL VASODILATOR REFLEXES PROJECTING THROUGH THE MYENTERIC PLEXUS

DE Reed, S Vanner

GI Diseases Research Unit, Queen’s University, Kingston, Ontario

In vivo models have established that intrinsic neural reflexes play a key role in regulating mucosal blood flow through activation of submucosal vasodilator neurons innervating submucosal arterioles, the major resistance vessels in the gastrointestinal tract. It is unclear however, where the sensory transduction occurs and whether pathways are confined to the submucosal plexus or are coordinated with motility pathways in the myenteric plexus. To address these questions, we developed a novel in vitro guinea pig ileum model using balloon distention of whole gut either within the intact lumen or beneath a flat sheet in the proximal portion and videomicroscopic recording of distention-evoked dilator responses of submucosal arterioles in the distal portion. Nifedipine was added to limit contraction of longitudinal/circular muscle layers. Distention-evoked dilator responses were recorded up to 2cm from the mid-balloon (n=40). Tetrodotoxin blocked all responses (n=9), demonstrating dilations were mediated by neural reflexes. The muscarinic antagonist 4-DAMP also blocked responses, implicating cholinergic submucosal vasodilator neurons. The projections of neural pathways were determined using surgical lesions to selectively sever the submucosal or myenteric plexus between recording and stimulating sites. Lesioning the submucosal plexus ~0.5-1.0cm from the recording site had no effect but responses were completely blocked by myenteric lesions. To establish whether sensory transduction can originate in the mucosa, preparations with or without the mucosa were compared. All preparations with mucosa responded to balloon distention compared to only 38% of those without. Mean dilator responses were 35% (% maximum vasodilation) with the mucosa intact and 14 % without (p= 0.035). Together, these studies demonstrate that mucosal sensory transduction mechanisms can respond to gut distention to trigger long descending neural vasodilator pathways. These pathways project through the myenteric plexus before projecting to the submucosal plexus, a mechanism which could coordinate motility and blood flow.

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