Please use this identifier to cite or link to this item: http://www.repositorio.ufop.br/handle/123456789/7863
Title: Discovery and characterization of Alamandine : a novel component of the Renin-Angiotensin system.
Authors: Lautner, Roberto Queiroga
Villela, Daniel Campos
Silva, Rodrigo Araújo Fraga da
Silva, Neiva Caldeira
Braga, Thiago Verano
Fraga, Fabiana Costa
Jankowski, Joachim
Jankowski, Vera
Sousa, Frederico Barros de
Alzamora, Andréia Carvalho
Soares, Everton Rocha
Barbosa, Claudiane Maria
Kjeldsen, Frank
Oliveira, Aline Cristina
Braga, Janaina Félix
Savergnini, Silvia Silveira Quintão
Etelvino, Gisele Maia
Peluso, Antonio Augusto Bastos
Silva, Danielle Gomes Passos
Ferreira, Anderson José
Alves, Fabiana
Martins, Almir de Sousa
Raizada, Mohan K.
Paula, Renata Dutra de
Santos, Daisy Motta
Klempin, Friederike
Pimenta, Adriano Monteiro de Castro
Alenina, Natalia
Millán, Ruben Dario Sinisterra
Bader, Michael
Santos, Maria José Campagnole dos
Santos, Robson Augusto Souza dos
Keywords: Antihypertensive treatment
Cardiovascular system
Hypertension
Vasoactive peptides
Vascular reactivity
Issue Date: 2013
Citation: LAUTNER, 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.
Abstract: The 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.
URI: http://www.repositorio.ufop.br/handle/123456789/7863
metadata.dc.identifier.uri2: http://circres.ahajournals.org/content/112/8/1104
ISSN: 15244571
Appears in Collections:DECBI - Artigos publicados em periódicos



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