GABAA receptor overexpression in the lateral hypothalamic area attenuates gastric ischemia-reperfusion injury in rats

Excessive activation of the greater splanchnic nerve (GSN) has previously been determined to contribute to the progression of gastric ischemia-reperfusion (GI-R) injury. The present study was designed to estimate the protective effects of GABA(A) receptor (GABA(A)R) overexpression in the lateral hypothalamic area (LHA) against GI-R injury. The GI-R injury model was induced in rats by clamping the celiac artery for 30 min and then reperfusing for 1 h. Microinjection of recombinant adenoviral vectors overexpressing GABA(A)R (Ad-GABA(A)R) or control adenoviral vectors (Ad-Con) into the LHA was conducted in GI-R and normal control rats. Significant protective effects were observed on day 2 after Ad-GABA(A)R treatment in the GI-R injury rats. Ad-GABA(A)R treatment reduced plasina norepinephrine levels, plasma angiotensin II levels and peripheral GSN activity, but increased the gastric mucosal blood flow, as compared with Ad-Con treatment. These results indicate that adenoviral vector-induced GABA(A)R overexpression in the LHA blunts GSN activity and subsequently alleviates the effects of gastric injury in GI-R rats.