Angiotensin-(1–7) is a major vasoactive metabolite of angiotensin II. The present study investigated the gastroprotective activity of exogenous angiotensin-(1–7) in rats exposed to water emersion and restraint stress. The restraint stress lesions were dose-dependently reduced by pretreatment with angiotensin-(1–7), which also caused an increase in gastric blood flow and the luminal content of NO. COX-1 and COX-2 inhibitors or l-NNA [N5-[imino(nitroamino)methyl]-l-ornithine] reversed the protection from angiotensin-(1–7). Angiotensin II augmented the stress induced gastrointestinal lesion, decreased gastric blood flow, and increased interleukin 1β (IL-1β) and tumor necrosis factor (TNF)-α levels. Capsaicin denervation attenuated the reduction of gastric lesions by angiotensin-(1–7). These results suggest that angiotensin-(1–7), in contrast to angiotensin II, affords potent gastroprotection against restraint stress-induced ulcerogenesis via increased blood flow mediated by NO, endogenous prostaglandins, sensory neuropeptides, and proinflammatory markers IL-1β and TNF-α.
See article at J Pharmacol Exp Ther 2013, 347:717–726.
- Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics