Sodium hydrogen exchanger as a mediator of hydrostatic edema-induced intestinal contractile dysfunction

Karen S. Uray, Shinil K. Shah, Ravi Radhakrishnan, Fernando Jimenez, Peter A. Walker, Randolph H. Stewart, Glen A. Laine, Charles S. Cox

Research output: Contribution to journalArticle

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Abstract

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. Conclusion: The mechanoresponsive ion channel NHE may mediate edema-induced intestinal contractile dysfunction, possibly via a STAT-3 related mechanism.

Original languageEnglish (US)
Pages (from-to)114-125
Number of pages12
JournalSurgery
Volume149
Issue number1
DOIs
StatePublished - Jan 2011
Externally publishedYes

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Sodium-Hydrogen Antiporter
Edema
Signal Transduction
Myosin Light Chains
Ion Channels
Phosphorylation
Smooth Muscle Myosins
Messenger RNA
Intestinal Mucosa
Resuscitation
Transcriptional Activation
Protein Isoforms
Proteins
Animal Models

ASJC Scopus subject areas

  • Surgery

Cite this

Uray, K. S., Shah, S. K., Radhakrishnan, R., Jimenez, F., Walker, P. A., Stewart, R. H., ... Cox, C. S. (2011). Sodium hydrogen exchanger as a mediator of hydrostatic edema-induced intestinal contractile dysfunction. Surgery, 149(1), 114-125. https://doi.org/10.1016/j.surg.2010.04.001

Sodium hydrogen exchanger as a mediator of hydrostatic edema-induced intestinal contractile dysfunction. / Uray, Karen S.; Shah, Shinil K.; Radhakrishnan, Ravi; Jimenez, Fernando; Walker, Peter A.; Stewart, Randolph H.; Laine, Glen A.; Cox, Charles S.

In: Surgery, Vol. 149, No. 1, 01.2011, p. 114-125.

Research output: Contribution to journalArticle

Uray, KS, Shah, SK, Radhakrishnan, R, Jimenez, F, Walker, PA, Stewart, RH, Laine, GA & Cox, CS 2011, 'Sodium hydrogen exchanger as a mediator of hydrostatic edema-induced intestinal contractile dysfunction', Surgery, vol. 149, no. 1, pp. 114-125. https://doi.org/10.1016/j.surg.2010.04.001
Uray, Karen S. ; Shah, Shinil K. ; Radhakrishnan, Ravi ; Jimenez, Fernando ; Walker, Peter A. ; Stewart, Randolph H. ; Laine, Glen A. ; Cox, Charles S. / Sodium hydrogen exchanger as a mediator of hydrostatic edema-induced intestinal contractile dysfunction. In: Surgery. 2011 ; Vol. 149, No. 1. pp. 114-125.
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