Increased blood pressure and water intake in transgenic mice expressing rat tonin in the brain

Increased blood pressure and water intake in transgenic mice expressing rat tonin in the brain

Author Cardoso, Cibele C. Google Scholar
Alenina, Natalia Google Scholar
Ferreira, Anderson J. Google Scholar
Qadri, Fatimunnisa Google Scholar
Lima, Mercia P. Google Scholar
Gross, Volkmar Google Scholar
Todiras, Mihail Google Scholar
Pesquero, Joao B. Autor UNIFESP Google Scholar
Pesquero, Jorge L. Google Scholar
Bader, Michael Google Scholar
Institution Max Delbruck Ctr Mol Med
Universidade Federal de Minas Gerais (UFMG)
Universidade Federal de São Paulo (UNIFESP)
Abstract Tonin is a serine proteinase of the kallikrein family that can produce angiotensin II directly from angiotensinogen. To clarify the importance of this enzyme for central nervous control of the cardiovascular system, we generated transgenic mice. TGM(rTon), that express rat tonin in astrocytes. These mice present high levels of tonin mRNA and activity specifically in the brain. As a consequence. TGM(rTon) develop increased blood pressure and water intake. Lisinopril, an ACE inhibitor, is less hypotensive for transgenic mice than for control animals. the AT(I) receptor antagonist candesartan equally lowers blood pressure in transgenic and in control mice. Plasma angiotensin II, but not angiotensin I, is increased in TGM(rTon) compared to the wild type, suggesting release of the peptide from the brain into the circulation. However. AT(I) receptors are desensitized in this transgenic model, as demonstrated by a blunted pressor response to intravenous application of angiotensin II. in conclusion, tonin in the brain may represent an alternative pathway for angiotensin II generation with effects on the cardiovascular system.
Keywords angiotensin II
blood pressure
transgenic mice
Language English
Date 2010-04-01
Published in Biological Chemistry. Berlin: Walter de Gruyter & Co, v. 391, n. 4, p. 435-441, 2010.
ISSN 1431-6730 (Sherpa/Romeo, impact factor)
Publisher Walter de Gruyter & Co
Extent 435-441
Access rights Closed access
Type Article
Web of Science ID WOS:000276338100014

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