Ischemic preconditioning attenuates gastric ischemia-reperfusion injury through involvement of glucocorticoids.

Abstract

Gastric ischemic preconditioning is one of the most effective approaches to attenuate the gastric mucosal injury caused by severe ischemia-reperfusion. In the present study we investigated whether glucocorticoid hormones participate in a realization of gastroprotective effect of ischemic preconditioning. Rats were exposed to prolonged gastric ischemia-reperfusion (30 min occlusion of celiac artery followed by 3 h of reperfusion) alone or with brief preliminary ischemic-reperfusion preconditioning (two 5 min episodes of occlusion of celiac artery followed by 10 min reperfusion). The experiments were carried out: 1) in adrenalectomized rats without or with corticosterone replacement and in sham-operated animals; 2) in rats pretreated by the inhibitor of glucocorticoid synthesis, metyrapone (30 mg/kg i.p.), and in control animals; 3) in rats pretreated by glucocorticoid receptors antagonist RU-38486 (20 mg/kg, p.o.) and in control animals. The prolonged ischemia-reperfusion resulted in the gastric injury. In control rats the brief ischemia-reperfusion (ischemic preconditioning) induced plasma corticosterone rise and attenuated the gastric lesions caused by prolonged ischemia-reperfusion. In adrenalectomized rats the gastroprotective effect of ischemic preconditioning was prevented but reversed by an acute corticosterone replacement (4 mg/kg, s.c.) applied immediately before ischemic preconditioning. Metyrapone pretreatment shortly inhibited corticosterone rise, caused by ischemic preconditioning, and prevented the gastroprotective action of ischemic preconditioning. The protective influence of ischemic preconditioning against gastric injury caused by prolonged ischemia-reperfusion was not observed in the rats pretreated by glucocorticoid receptors antagonist RU-38486. The results suggest that glucocorticoid hormones participate in a realization of the protective effects of ischemic preconditioning in gastric mucosa.