title: Hypertonic saline alters hydraulic conductivity and up-regulates mucosal/submucosal aquaporin 4 in resuscitation-induced intestinal edema.
abstract: OBJECTIVE
  To characterize membrane conductivity by applying mathematical modeling techniques and immunohistochemistry and to localize and predict areas of the bowel where aquaporins may be associated with edema resolution/prevention associated with hypertonic saline. Intestinal edema induced by resuscitation and mesenteric venous hypertension impairs intestinal transit/contractility. Hypertonic saline decreases intestinal edema and improves transit. Aquaporins are water transport membrane proteins that may be up-regulated with edema and/or hypertonic saline.
  
  
  METHODS
  Laboratory study.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  Male Sprague Dawley rats, weighing 270 to 330 g.
  
  
  METHODS
  Rats were randomized to control (with and without hypertonic saline) and mesenteric venous hypertension with either 80 mL/kg normal saline (RESUS + VH + VEH) or 80 mL/kg normal saline with hypertonic saline (RESUS + VH + HTS). After 6 hrs, intestinal wet/dry ratios, urine output, peritoneal fluid, and intraluminal fluid were measured. Hydraulic conductivity was calculated from our previously known and published pressure-flow data. The cDNA microarray, Western blot, polymerase chain reaction, and immunohistochemistry studies were conducted for candidate aquaporins and distribution in intestinal edema resolution.
  
  
  RESULTS
  Hypertonic saline decreased edema and increased urine, intraluminal, and peritoneal fluid volume. RESUS + VH favors fluid flux into the interstitium. Hypertonic saline causes increased hydraulic conductivity at the seromuscular and mucosal surfaces at the same time limiting flow into the interstitium. This is associated with increased aquaporin 4 expression in the intestinal mucosa and submucosa.
  
  
  CONCLUSIONS
  Hypertonic saline mitigates intestinal edema development and promotes fluid redistribution secondary to increased membrane conductivity at the mucosal and seromuscular surfaces. This is associated with up-regulation of aquaporin 4 gene expression and protein. Aquaporin 4 may be a useful therapeutic target for strategies to enhance edema resolution.
authors.affiliation: Department of Pediatric Surgery and Trauma Research Center, University of Texas Medical School at Houston, Houston, TX, USA.
authors.forename: Ravi S
authors.initials: RS
authors.lastname: Radhakrishnan
authors.forename: Shinil K
authors.initials: SK
authors.lastname: Shah
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Lance
authors.forename: Hari R
authors.initials: HR
authors.lastname: Radhakrishnan
authors.forename: Hasen
authors.initials: H
authors.lastname: Xue
authors.forename: Geetha L
authors.initials: GL
authors.lastname: Radhakrishnan
authors.forename: Uma S
authors.initials: US
authors.lastname: Ramaswamy
authors.forename: Peter A
authors.initials: PA
authors.lastname: Walker
authors.forename: Karen S
authors.initials: KS
authors.lastname: Uray
authors.forename: Glen A
authors.initials: GA
authors.lastname: Laine
authors.forename: Randolph H
authors.initials: RH
authors.lastname: Stewart
authors.forename: Charles S
authors.initials: CS
authors.lastname: Cox
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism*; D001202:Ascitic Fluid; D001692:Biological Transport; D004487:Edema / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D007150:Immunohistochemistry; D007410:Intestinal Diseases / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation / Q000009:adverse effects; D012462:Saline Solution, Hypertonic / Q000493:pharmacokinetics*; D015854:Up-Regulation; D014556:Urine
chemical_list: C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D012462:Saline Solution, Hypertonic