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Increased RAS activity leading to increase in Ang II levels, may increase the risk of developing PD, AD, HD or MS. However, the alteration in the balance among angiotensin peptides resulting in increasing Ang-(1-7) or Alamandine may represent effective neuroprotective strategy in population groups at high risk or as coadjutant treatment to reduce the progression of these diseases. Although most studies suggest a neuroprotective action for ACE inhibition or AT1 receptor antagonism, many studies will still be needed to characterize the relative importance (and intracellular mechanisms) of each RAS peptide for the pathophysiology of neurodegenerative diseases. The results to date are promising and may lead to new and more effective pharmacological tools to prevent and better control neurodegenerative diseases.

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Angiotensin-(1-7) [Ang-(1-7)], a counter-regulatory peptide of the renin-angiotensin system (RAS) exerts its effects through the G-protein-coupled receptor Mas, which is expressed in different tissues, including the brain. Ang-(1-7) has a broad range of effects beyond the well-described cardiovascular and renal actions, including the modulation of emotional and behavioural responses. In the present study we tested the hypothesis that Ang-(1-7) could attenuate the anxiety- and depression-like behaviours observed in transgenic hypertensive (mRen2)27 rats (TGRs). We also hypothesized that Ang-(1-7) could be involved in the anxiolytic-like effect induced by ACE (angiotensin-converting enzyme) treatment in these hypertensive rats. Therefore, TGRs and Sprague-Dawley rats were subjected to the Elevated Plus Maze (EPM) test, Forced Swimming Test (FST) and Novelty Suppressed Feeding (NSF). TGRs presented a decreased percentage of entries in the open arms of the EPM test, a phenotype reversed by systemic treatment with enalapril or intracerebroventricular infusion of Ang-(1-7). It is interesting that pre-treatment with A779, a selective Mas receptor antagonist, prevented the anxiolytic-like effect induced by the ACE inhibitor. In the NSF test, TGRs showed increased latency to eating, an indicative of a higher aversion in response to a new environment. These animals also showed increased immobility in the FST. Again, Ang-(1-7) reversed this phenotype. Thus, our data showed that Ang-(1-7) can modulate anxiety- and depression-like behaviours in TGRs and warrant further investigation as a new therapy for certain psychiatric disorders.

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