Gastric Adaptation to Stress: Role of Sensory Nerves, Salivary Glands, and Adrenal Glands

Abstract

Background: Single exposure to water immersion and restraint stress (WRS) in rats produces acute gastric mucosal damage, but repetitive WRS insults lead to gastric adaptation to stress ulcerogenesis. This study was designed to assess the mechanism of this adaptation, particularly the role of sensory nerves, salivary glands, adrenal glands, and gastric acid secretion. Methods: WRS was applied for a standard period of 3.5 h, either once or repeated every other day for up to 8 days in intact rats and in animals with capsaicin-induced deactivation of sensory nerves, vagotomy, salivectomy, adrenalectomy, and inhibition of gastric acid secretion by H₂-blocker. Results: WRS applied once produced multiple gastric erosions accompanied by a significant increase in gastric acid secretion and a decrease in gastric blood flow (GBF) and DNA synthesis. Repeated WRS insults resulted in a significant decrease in the number of gastric lesions, reaching a maximum after four consecutive exposures to WRS. This adaptation to stress ulcerogenesis was accompanied by a decrease in gastric acid secretion and an increase in GBF and mucosal generation of DNA synthesis. Salivectomy, which decreased the luminal content of epidermal growth factor (EGF) (by about 80%), markedly attenuated this adaptation, and this was reversed by the addition of exogenous EGF. Capsaicin-induced ablation of sensory nerves eliminated gastric adaptation to WRS, and this was accompanied by a significant decrease in the GBF, but pretreatment with calcitonin gene-related peptide restored gastric adaptation to stress in capsaicin-denervated rats. Selective vagotomy and adrenalectomy failed to affect gastric adaptation to WRS, whereas gastric acid inhibition by ranitidine enhanced this adaptation. Conclusions: The stomach is able to adapt to repeated stress insults by enhancing GBF and DNA synthesis, and this adaptation is mediated, at least in part, by sensory nerves and EGF.

Key Words:

• Calcitonin gene-related peptide
• epidermal growth factor
• gastric blood flow
• sensory neurons
• stress
• vagus