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Increased angiotensin II formation in the brain modulates cardiovascular homeostasis and erythropoiesis

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Item Type:Article
Title:Increased angiotensin II formation in the brain modulates cardiovascular homeostasis and erythropoiesis
Creators Name:Rodrigues, A.F. and Todiras, M. and Qadri, F. and Campagnole-Santos, M.J. and Alenina, N. and Bader, M.
Abstract:In spite of the fact that the modulatory effects of angiotensin II (Ang II) on the sympathetic nerve activity to targeted organs involved in blood pressure (BP) regulation is well acknowledged, the local production of this peptide in the brain and the consequences of enhanced central Ang II beyond the cardiovascular system are not yet well comprehended. In this study, we generated and validated a new transgenic mouse line overexpressing the rat full-length angiotensinogen (Agt) protein specifically in the brain (Agt-Tg). Adult Agt-Tg mice presented overall increased gene expression of total Agt in the brain including brainstem and hypothalamus. In addition, the excess of Agt led to abundantly detectable brain Ang II levels as well as increased circulating copeptin levels. Agt-Tg displayed raised BP in acute recordings, while long-term telemetrically measured basal BP was indistinguishable from wildtypes. Agt-Tg has altered peripheral renin angiotensin system and vasomotor sympathetic tone homeostasis, because renal gene expression analysis, plasma Ang II measurements and ganglionic blockade experiments revealed suppressed renin expression, reduced Ang II and higher neurogenic pressure response, respectively. Plasma and urine screens revealed apparently normal fluid and electrolyte handling in Agt-Tg. Interestingly, hematological analyses showed increased hematocrit in Agt-Tg caused by enhanced erythropoiesis, which was reverted by submitting the transgenic mice to a long-term peripheral sympathectomy protocol. Collectively, our findings suggest that Agt-Tg is a valuable tool not only to study brain Ang II formation and its modulatory effects on cardiovascular homeostasis but also its role in erythropoiesis control via autonomic modulation.
Keywords:Brain RAS, Neurophysiology, Blood Pressure, Sympathetic System, Red Blood Cells, Animals, Mice
Source:Clinical Science
Publisher:Portland Press
Page Range:1353-1367
Date:2 June 2021
Additional Information:Copyright © 2021 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
Official Publication:https://doi.org/10.1042/CS20210072
PubMed:View item in PubMed

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