Mechanisms Underlying the Gastroprotective Action of Glucocorticoids Released in Response to Ulcerogenic Stress Factors

Abstract

Our previous results demonstrate the gastroprotective but not ulcerogenic action of glucocorticoids released in response to ulcerogenic stress factors. The present study was undertaken to investigate the possible mechanisms underlying the gastroprotective action of glucocorticoids in rat stomachs. The effects of deficiency of glucocorticoid production, with or without corticosterone supplementation, on blood flow velocity in gastric microvessels, microvascular permeability, mucus production, motility as well as gastric lesions were studied 3 to 4 h after the onset of ulcerogenic stimuli: water-restraint stress or indomethacin administration. The contribution of glucocorticoids in the healing process of gastric injury was also evaluated. The deficiency in glucocorticoid production significantly potentiated the functional disorders induced by ulcerogenic stimuli, such as a decrease in blood flow velocity and mucus production and an increase in gastric motility and in microvascular permeability, which resulted in aggravation of the formation of gastric lesions as well as impairment of their healing. The changes observed were prevented by supplementation of corticosterone at a dose mimicking a stress-induced corticosterone rise. We conclude that a gastroprotective action of glucocorticoids may be provided by multiple actions, including maintenance of the gastric mucosal blood flow and mucus production, attenuation of the enhanced gastric motility and microvascular permeability as well as beneficial influences on healing processes.

Gastroprotective Role of Glucocorticoid Hormones

“…Using in vivo microscopy to directly visualize the gastric microcirculation, we examined the effects of a deficiency of stress-induced glucocorticoid production as well as corticosterone replacement in anesthetized rats after ulcerogenic stress. The deficiency of glucocorticoids during water immersion-restraint stress promoted the stress-induced decrease of blood flow velocity in submucosal and mucosal microvessels, the effect being prevented by corticosterone replacement (13,14). These results suggest that the gastroprotective actions of glucocorticoids during stress may be partly due to the maintenance of gastric mucosal blood flow that may be brought about by the effect on arterial blood pressure (13,14).…”

“…Glucocorticoids (29) and these afferent neurons (30) are known to be involved in glucostasis during hypoglycemia. Moreover, both of these factors contribute to gastroprotection through a beneficial influence on gastric mucosal blood flow (13,14,27). The simultaneous removal of the beneficial action of both factors on these targets might explain why severe gastric damage occurs in adrenalectomized rats with desensitization of capsaicin-sensitive afferent neurons.…”

“…Mersereau and Hinchey (24) reported a role for the glycoprivic response in the mechanism of gastric hypermotility induced by NSAIDs. To clarify the mechanisms underlying the gastroprotective action of glucocorticoids against indomethacin-induced injury, we investigated the effect of adrenalectomy with or without corticosterone replacement on blood glucose levels, gastric motility, microvascular permeability, blood flow velocity in gastric submucosal and mucosal microvessels, and mucus secretion before and after the administration of indomethacin at an ulcerogenic dose (14,17,25). Indomethacin caused gastric erosion in sham-operated rats, with an increase in gastric motility and microvascular permeability as well as a decrease in the blood glucose level, mucus secretion, and blood flow velocity in gastric submucosal and mucosal microvessels (Fig.…”

Activation of the Hypothalamic-Pituitary-Adrenocortical Axis as a Gastroprotective Component of Stress Response

“…Water immersion-restraint stress caused decrease in blood flow velocity in submucosal and mucosal gastric microvessels. The deficiency of glucocorticoids during water immersionrestraint stress promoted the stress-induced decrease of blood flow velocity in submucosal and mucosal microvessels, and corticosterone replacement prevented this effect (Filaretova et al 1999(Filaretova et al , 2004. The results suggest that glucocorticoids released during water immersionrestraint stress maintain gastric blood flow during the stress.…”

“…It means that the improvement of gastric blood supply by glucocorticoids is provided, at least partly, through their beneficial action on systemic blood circulation. The data suggests that the gastroprotective actions of glucocorticoids during water immersion-restraint stress may be provided by the maintenance of gastric blood flow that may be brought about by their beneficial effect on arterial blood pressure (Filaretova et al 1999(Filaretova et al , 2004. Thus, glucocorticoids released during activation of the HPA axis may contribute to protection of the gastric mucosa by maintaining general body homeostasis, including glucose levels and systemic blood pressure, which could be a basis for their beneficial influence on gastric mucosal integrity.…”