Objective: 

The aim of the study is to investigate the role of gastric mucosal blood flow in the protective effect of orexin-A (OXA) on ischemia/reperfusion (I/R)-induced gastric mucosal injury.

Methods: 

Three main experimental groups were arranged: Sham, I/R and I/R+OXA. I/R was applied for I/R+saline, I/R+capsaicin, I/R+L-NAME and I/R+vagotomy subgroups while additional OXA infusion was applied for I/R+capsaicin+OXA, I/R+L-NAME+OXA, I/R+vagotomy+OXA subgroups. In sham group, saline infusion (0.01 ml/kg.min) was applied through the jugular vein simultaneously with 3.5 hours of I/R. For I/R+OXA groups, 500 pmol/kg.min of OXA was administered at the same rate. Capsaicin (125 mg/kg, s.c.) was used for sensory nerve denervation while L-NAME (30 mg/kg, i.v.) was administered as nitric oxide synthase (NOS) inhibitor. 24 hours prior to I/R and/or OXA application, subdiaphragmatic bilateral vagotomy was performed to the vagotomy group animals. Following I/R application at each group, stomachs were taken out and opened through the greater curvature. Mucosal blood flow was measured by Laser Doppler Flowmeter and lesion index was determined under stereomicroscopy.

Results: 

I/R-induced gastric mucosal damage was significantly decreased and blood flow was increased in OXA group. No significant difference was observed for either lesion index or blood flow in I/R+Capsaicin and I/R+L-NAME groups compared to I/R group. Lesion index was significantly increased while mucosal blood flow was decreased in I/R+Capsaicin+OXA, I/R+L-NAME+OXA and I/R+Vagotomy+OXA groups compared to I/R+OXA group. For each of these three groups, protective effect of OXA diminished and the outcomes approximated to I/R group.

Conclusions: 

In conclusion, the increased level of mucosal blood flow is effective in the OXA-mediated gastric mucosal protection.