Inhibition of intestinal transit by resuscitation-induced gut edema is reversed by L-NIL.
BACKGROUND
Post-resuscitation gut edema and associated gut dysfunction is a common and significant clinical problem that occurs after traumatic injury and shock. We have shown previously that gut edema without ischemia/reperfusion injury delays intestinal transit [1]. We hypothesized that gut edema increases expression of inducible nitric oxide synthase (iNOS) protein, and that selective iNOS inhibition using L-NIL reverses the delayed intestinal transit associated with gut edema.


METHODS
One hour prior to laparotomy, rats were pretreated with 10 mg/kg body weight of intraperitoneal L-NIL or saline vehicle and underwent 80 ml/kg body weight of 0.9% saline + superior mesenteric venous pressure elevation (Edema) or sham surgery (Sham). A duodenal catheter was placed to allow injection of a fluorescent dye for the measurement of intestinal transit. At 6 h, the small bowel was divided and the mean geometric center (MGC) of fluorescent dye was measured to determine transit. Ileum was harvested for histological assessment of mucosal injury, evaluation of iNOS protein expression by Western blotting, and MPO activity. Tissue water was determined using the wet-to-dry weight ratio to assess gut edema. Data are expressed as mean +/- SEM, n = 3-6 and * = P <0.05 using ANOVA.


RESULTS
Gut edema, expressed as increased wet-to-dry ratio, was associated with decreased intestinal transit and elevated iNOS protein expression. Pretreatment with l-NIL improved intestinal transit and decreased expression of iNOS protein without decreasing intestinal tissue water compared to edema animals. There was no difference in mucosal injury or MPO activity among groups.


CONCLUSIONS
Gut edema delays intestinal transit via an iNOS-mediated mechanism.
Department of Surgery, University of Texas-Houston Medical School, Houston, Texas 77030, USA.
S D
SD
Moore-Olufemi
H
H
Xue
S J
SJ
Allen
F A
FA
Moore
R H
RH
Stewart
G A
GA
Laine
C S
CS
Cox
D000818:Animals; D015153:Blotting, Western; D001834:Body Water; D004487:Edema / Q000150:complications / Q000201:enzymology* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005456:Fluorescent Dyes; D005772:Gastrointestinal Transit / Q000187:drug effects; D045823:Ileus / Q000188:drug therapy* / Q000209:etiology; D007410:Intestinal Diseases / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D008239:Lysine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation / Q000009:adverse effects*
D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; C090663:N(6)-(1-iminoethyl)lysine; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; D008239:Lysine