Lautner, Roberto QueirogaVillela, Daniel CamposSilva, Rodrigo Araújo Fraga daSilva, Neiva CaldeiraBraga, Thiago VeranoFraga, Fabiana CostaJankowski, JoachimJankowski, VeraSousa, Frederico Barros deAlzamora, Andréia CarvalhoSoares, Everton RochaBarbosa, Claudiane MariaKjeldsen, FrankOliveira, Aline CristinaBraga, Janaina FélixSavergnini, Silvia Silveira QuintãoEtelvino, Gisele MaiaPeluso, Antonio Augusto BastosSilva, Danielle Gomes PassosFerreira, Anderson JoséAlves, FabianaMartins, Almir de SousaRaizada, Mohan K.Paula, Renata Dutra deSantos, Daisy MottaKlempin, FriederikePimenta, Adriano Monteiro de CastroAlenina, NataliaSinisterra Millán, Ruben DarioBader, MichaelSantos, Maria José Campagnole dosSantos, Robson Augusto Souza dos2017-06-022017-06-022013LAUTNER, R. Q. et al. Discovery and characterization of Alamandine: a novel component of the Renin-Angiotensin system. Circulation Research, v. 112, p. 1104, 2013. Disponível em: <http://circres.ahajournals.org/content/112/8/1104>. Acesso em: 19 fev. 2017.1524-4571http://www.repositorio.ufop.br/handle/123456789/7863The renin–angiotensin system (RAS) is a key regulator of the cardiovascular system, electrolyte, and water balance. Here, we report identification and characterization of alamandine, a new heptapeptide generated by catalytic action of angiotensin-converting enzyme-2 angiotensin A or directly from angiotensin-(1–7). To characterize a novel component of the RAS, alamandine. Using mass spectrometry we observed that alamandine circulates in human blood and can be formed from angiotensin-(1–7) in the heart. Alamandine produces several physiological actions that resemble those produced by angiotensin-(1–7), including vasodilation, antifibrosis, antihypertensive, and central effects. Interestingly, our data reveal that its actions are independent of the known vasodilator receptors of the RAS, Mas, and angiotensin II type 2 receptor. Rather, we demonstrate that alamandine acts through the Mas-related G-protein–coupled receptor, member D. Binding of alamandine to Mas-related G-protein–coupled receptor, member D is blocked by D-Pro7-angiotensin-(1–7), the Mas-related G-protein–coupled receptor, member D ligand β-alanine and PD123319, but not by the Mas antagonist A-779. In addition, oral administration of an inclusion compound of alamandine/β-hydroxypropyl cyclodextrin produced a long-term antihypertensive effect in spontaneously hypertensive rats and antifibrotic effects in isoproterenol-treated rats. Alamandine had no noticeable proliferative or antiproliferative effect in human tumoral cell lines. The identification of these 2 novel components of the RAS, alamandine and its receptor, provides new insights for the understanding of the physiological and pathophysiological role of the RAS and may help to develop new therapeutic strategies for treating human cardiovascular diseases and other related disorders.en-USrestritoAntihypertensive treatmentCardiovascular systemHypertensionVasoactive peptidesVascular reactivityArtigo publicado em periodicohttp://circres.ahajournals.org/content/112/8/1104https://doi.org/10.1161/CIRCRESAHA.113.301077