Mice lacking the [Na.sup.+]/[H.sup.+] exchanger 2 have impaired recovery of intestinal barrier function

Ischemic injury induces breakdown of the intestinal barrier. Recent studies in porcine postischemic tissues indicate that inhibition of NHE2 results in enhanced recovery of barrier function in vitro via a process involving interepithelial tight junctions. To further study this process, recovery of barrier function was assessed in wild-type (NHE[2.sup.+/+]) and NHE[2.sup.-/-] mice in vivo and wild-type mice in vitro. Mice were subjected to complete mesenteric ischemia in vivo, after which barrier function was measured by blood-to-lumen mannitol clearance over a 3-h recovery period or measurement of transepithelial electrical resistance (TER) in Ussing chambers immediately following ischemia. Tissues were assessed for expression of select junctional proteins. Compared with NHE[2.sup.+/+] mice, NHE[2.sup.-/-] mice had greater intestinal permeability during the postischemic recovery process. In contrast to prior porcine studies, pharmacological inhibition of NHE2 in post-ischemic tissues from wild-type mice also resulted in significant reductions in TER. Mucosa from NHE[2.sup.-/-] mice displayed a shift of occludin and claudin-1 expression to the Triton-X-soluble membrane fractions and showed disruption of occludin and claudin-1 localization patterns following injury. This was qualitatively and quantitatively recovered in NHE[2.sup.+/+] mice compared with NHE[2.sup.-/-] mice by the end of the 3-h recovery period. Serine phosphorylation of occludin and claudin-1 was downregulated in NHE[2.sup.-/-] postischemia compared with wild-type mice. These data indicate an important role for NHE2 in recovery of barrier function in mice via a mechanism involving tight junctions. tight junction; intestinal permeability; ischemia; [Na.sup.+]/[H.sup.+] exchange