Transforming Non‐Ulcerogenic Stress Stimuli into Gastric Ulcerogenic Ones under the Circumstances of Inhibition of the Hypothalamic‐Pituitary‐Adrenocortical Axis

Abstract

To investigate contribution of glucocorticoids to the maintenance of gastric mucosal integrity during stress we predominantly used ulcerogenic stress models. Using these models we demonstrated that glucocorticoids released in response to the ulcerogenic stimuli attenuated their harmful action on the gastric mucosa.In the present study we hypothesized that mild stressors does not damage the gastric mucosa due to gastroprotective action of glucocorticoids released in response to these stimuli. To verify the hypothesis the effects of normally non‐ulcerogenic mild stimuli (15‐30 min cold‐restraint) on the gastric mucosa have been studied under the circumstances of inhibition ofthe hypothalamic‐pituitary‐adrenocortical (HPA) axis in rats. The HPA axis was inhibited by: 1) fast inhibitory action of NBI 27914, the selective antagonist of cortricotropin‐releasing factor receptor type 1; 2) fast inhibitory action of metyrapone, inhibitor glucocoricoid synthesis; 3) delayed inhibitory action of a single pharmacological dose of cortisol injected one week before the onset of stress stimulus. Each of these pretreatments decreased 15‐30 min cold‐restraint‐produced corticosterone levels and resulted in an appearance of gastric lesions after the onset of this mild stress. The results suggest that in rats with glucocorticoid deficiency non‐ulcerogenic stimuli are transformed into ulcerogenic ones and confirm the hypothesis. The findings further support for the point of view that glucocorticoids released during acute stress are gastroprotective factors. Supported by the Russian Scientific Foundation (grant N 14‐15‐00790).