The role of altered intestinal permeability in the pathogenesis of salmonella diarrhea in the rhesus monkey.
The pathogenesis of Salmonella diarrhea is unclear. Bacterial invasion of the ileal and colonic mucosa resulting in an intense ileocolitis regularly occurs in concert with secretion of water and sodium in jejunum, ileum, and colon. To examine the role of altered permeability in Salmonella diarrhea we studied intestinal histology, water and electrolyte transport, clearance of intravenously injected [14C]erythritol and [3H]mannitol, and changes in transmural electrical potential difference in normal and Salmonella-infected rhesus monkeys. In normal animals, absorption of water and sodium occurred in jejunum, ileum, and colon and a gradient of diminishing permeability from jejunum to ileum to colon for both erythritol and mannitol was observed. Permeability as measured by determining permeability coefficients was not increased by Salmonella infection and in fact was significantly reduced for erythritol in the jejunum of infected animals. Perfusion with hypertonic erythritol and mannitol produced the same streaming potentials (deltaPD) in control and infected animals, indicating no differences in transmucosal permeability. As a positive control, perfusion with 25 mM ethylenediaminetetraacetic acid in normal animals increased permeability, resulting in increased plasma-to-lumen isotope flux and no deltaPD in response to hypertonic perfusates. These data show that despite severe alterations in intestinal histology, transmucosal permeability remains unchanged and thus is not a contributing factor in Salmonella diarrhea.
D000818:Animals; D001834:Body Water / Q000378:metabolism; D002463:Cell Membrane Permeability; D002766:Cholecystokinin / Q000494:pharmacology; D003967:Diarrhea / Q000378:metabolism / Q000473:pathology*; D004896:Erythritol / Q000378:metabolism; D000882:Haplorhini; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D008297:Male; D008353:Mannitol / Q000378:metabolism; D008564:Membrane Potentials; D009638:Norepinephrine / Q000494:pharmacology; D012480:Salmonella Infections / Q000378:metabolism / Q000473:pathology*; D012486:Salmonella typhimurium / Q000472:pathogenicity; D012964:Sodium / Q000378:metabolism
D008353:Mannitol; D002766:Cholecystokinin; D012964:Sodium; D004896:Erythritol; D009638:Norepinephrine