Involvement of Renin-Angiotensin System and Vasoactive Angiotensin-(1-7) Metabolite of Angiotensin II in Gastric Mucosal Injury and Gastroprotection

The renin-angiotensin system (RAS) plays an important role in the maintenance of blood pressure, cardiovascular functions, body fluids homeostasis and kidney reabsorption process but little is known whether angiotensin derivative metabolites, the classic component of the systemic and local RAS exhibit gastroprotective and ulcer healing properties. Angiotensin II (Ang II) formed from angiotensin I due to angiotensin-converting enzyme (ACE) binds to the Ang type 1 (AT1) and type 2 (AT2) receptors, both implicated in the pathogenesis of cold stress- and ischemia-reperfusion-induced gastric lesions. The new functional components of RAS, such as Ang-(1-7), Ang IV, Ang-(1-12) and novel pathways ACE2 have been recently proposed to maintain physiological functions in the gastrointestinal (GI) tract. In this review, we describe the contribution of the Ang II metabolite, Ang-(1-7), to gastroprotection against stress-induced gastric lesions. First, Ang-(1-7) is produced in excessive amounts in the gastric mucosa of rodents, suggesting that this metabolite could be involved in the mechanism of gastric mucosal defense. Second, pretreatment with Ang(1-7) attenuated the gastric lesions induced by cold-restraint stress and raised the gastric blood flow, suggesting that this vasoactive metabolite of Ang II could be involved in the mechanism of gastric integrity and gastroprotection. This protective response can be demonstrated in experimental damage induced by acid-dependent (stress, ischemia-reperfusion) and acid-independent (ethanol) injury. We conclude that full understanding of the metabolic pathways of Ang I and Ang II conversion into vasoactive metabolites such as Ang-(1-7) in the stomach and the efficacy of Ang-(1-7) to attenuate gastric lesions induced by damaging agents may be useful in the treatment of upper Cl disorders including the mechanism of protection against mucosal damage induced by various ulcerogens and in the process of ulcer healing. Copyright (C) 2012 S. Karger AG, Basel