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

Item Type:Article
Title:Increased blood pressure and water intake in transgenic mice expressing rat tonin in the brain
Creators Name:Cardoso, C.C. and Alenina, N. and Ferreira, A.J. and Qadri, F. and Lima, M.P. and Gross, V. and Todiras, M. and Pesquero, J.B. and Pesquero, J.L. and Bader, M.
Abstract:Tonin is a serine proteinase of the kallikrein family able to produce angiotensin II directly from angiotensinogen. In order to clarify the importance of this enzyme for the central nervous control of the cardiovascular system, we have generated transgenic mice, TGM(rTon), which 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(1) 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) as compared to the wild type suggesting a release of the peptide from the brain into the circulation. However, AT(1) receptors are desensitized in this transgenic model as shown by a blunted pressor response to intravenous application of angiotensin II. In conclusion, tonin in the brain may represent an alternative pathway to generate angiotensin II with effects on the cardiovascular system.
Keywords:Angiotensin II, Blood Pressure, Tonin, Transgenic Mice, Animals, Mice, Rats
Source:Biological Chemistry
ISSN:1431-6730
Publisher:de Gruyter (Germany)
Volume:391
Number:4
Page Range:435-441
Date:April 2010
Official Publication:https://doi.org/10.1515/BC.2010.040
PubMed:View item in PubMed

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