Role of sensory afferent nerves and nitric oxide in Orexin-A-induced gastroprotection against ischemia-reperfusion injury

The aim of the study was to investigate the roles of sensory innervation and NO mediated system in protective mechanisms of Orexin-A (OXA) against ischemia/reperfusion (I/R) induced gastric injury. For this purpose, a Sham group and several I/R groups were formed. OXA groups received 500 pmol/kg/min of OXA infusion.Gastric mucosal injury caused by I/R significantly reduced in OXA infused rats while the blood flow increased. Protective effect of OXA diminished in I/R groups those received L-NAME, capsaicin or vagotomy application. MPO enzyme activity significantly increased with I/R, but decreased with OXA infusion. However, when these agents were applied with OXA infusion, the decline in MPO activity which was observed after sole OXA infusion was diminished. CGRP level was lower in I/R group, but significantly increased following OXA infusion. L-NAME, capsaicin and vagotomy caused significant decrease in CGRP levels compared to the level at OXA group. Nitrite/nitrate (NOx) level increased with I/R and OXA infusion did not change it. L-NAME application significantly decreased NOx level. NOx levels of groups those received L-NAME and capsaicin before OXA infusion were significantly lower than the OXA group. I/R increased iNOS protein expression in gastric tissue. It decreased significantly in the OXA and L-NAME groups. eNOS protein expression significantly decreased with I/R while there was no change in groups those received OXA or L-NAME with I/R.In conclusion, it has been shown that sensory afferent neurons and nitric oxide mediate the protective mechanisms of OXA against I/R related gastric mucosal injuries.