Angiotensin (1-7) protects against stress-induced gastric lesions in rats

Stress ulcers can develop with severe physiological stress, and have been proposed as being brain-driven events. New findings continue to suggest that stress ulcers can be more effectively managed through central manipulation rather than by simply altering local gastric factors. Angiotensin (1-7) (Ang (1-7)) is present as an endogenous constituent of the brain and stomach. The beneficial effects of Ang (1-7) have been confirmed in the vessels, brain, heart, kidney, liver and lungs, but not in the stomach. Given the accumulating evidence suggesting the anti-stress activities of Ang (1-7), its potential gastroprotective effect in the context of stress requires further investigation. In the present study, rat gastric mucosal lesions were induced by 2h of cold-restraint stress. We observed that these lesions were significantly attenuated after 1 week of intracerebroventricular treatment with Ang (1-7). This gastroprotective effect was associated with attenuated oxidative stress and suppressed acid secretion. Brain Ang (1-7) administration profoundly modified responses to stress, indicated by altered levels of several stress hormones, including Ang II, glucocorticoid, norepinephrine, serotonin, and dopamine, in blood or stress-related brain regions. These findings indicate that Ang (1-7) exerts anti-stress activities by restoring the gastric microenvironment and modulating the stress pathways. Ang (1-7) may be a promising agent for stress ulcer prophylaxis and therapy, administered through brain-permeable mimics or carriers.