Sodium hydrogen exchanger as a mediator of hydrostatic edema-induced intestinal contractile dysfunction.
BACKGROUND
Resuscitation-induced intestinal edema is associated with early and profound mechanical changes in intestinal tissue. We hypothesize that the sodium hydrogen exchanger (NHE), a mechanoresponsive ion channel, is a mediator of edema-induced intestinal contractile dysfunction.


METHODS
An animal model of hydrostatic intestinal edema was used for all experiments. NHE isoforms 1-3 mRNA and protein were evaluated. Subsequently, the effects of NHE inhibition (with 5-(N-ethyl-N-isopropyl) amiloride [EIPA]) on wet-to-dry ratios, signal transduction and activator of transcription (STAT)-3, intestinal smooth muscle myosin light chain (MLC) phosphorylation, intestinal contractile activity, and intestinal transit were measured.


RESULTS
NHE1-3 mRNA and protein levels were increased significantly in the small intestinal mucosa with the induction of intestinal edema. The administration of EIPA, an NHE inhibitor, attenuated validated markers of intestinal contractile dysfunction induced by edema as measured by decreased STAT-3 activation, increased MLC phosphorylation, improved intestinal contractile activity, and enhanced intestinal transit.


CONCLUSIONS
The mechanoresponsive ion channel NHE may mediate edema-induced intestinal contractile dysfunction, possibly via a STAT-3 related mechanism.
Uray
Karen S
KS
Department of Pediatric Surgery, University of Texas Medical School at Houston, Houston, TX 77030, USA.
Shah
Shinil K
SK
Radhakrishnan
Ravi S
RS
Jimenez
Fernando
F
Walker
Peter A
PA
Stewart
Randolph H
RH
Laine
Glen A
GA
Cox
Charles S
CS
D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D004487:Edema / Q000209:etiology / Q000503:physiopathology*; D005455:Fluorescent Antibody Technique; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000235:genetics; D006874:Hydrostatic Pressure; D007410:Intestinal Diseases / Q000503:physiopathology; D007813:Laparotomy / Q000379:methods; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D012016:Reference Values; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012680:Sensitivity and Specificity; D015398:Signal Transduction; D017923:Sodium-Hydrogen Exchangers / Q000187:drug effects / Q000378:metabolism*
D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D017923:Sodium-Hydrogen Exchangers; C494088:Stat3 protein, rat; D000584:Amiloride; C039614:ethylisopropylamiloride