Genetic ablation of angiotensinogen in the subfornical organ of the brain prevents the central angiotensinergic pressor response.

Genetic ablation of angiotensinogen in the subfornical organ of the brain prevents the central angiotensinergic pressor response. Research Abstract Details 

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Genetic ablation of angiotensinogen in the subfornical organ of the brain prevents the central angiotensinergic pressor response. Abstract Text:

Puspha Sinnayah,Eric Lazartigues,Koji Sakai,Ram V Sharma,Curt D Sigmund,Robin L Davisson,

The subfornical organ (SFO) of the brain has long been considered a critical integrating center for the cardiovascular actions of the renin-angiotensin system (RAS). Early reports of angiotensin II (Ang II) immunoreactivity in the SFO and its neural projections to downstream cardiovascular nuclei raised the possibility that Ang II is produced locally and functions as a putative neurotransmitter in these circuits. However, evidence of functionally significant de novo synthesis of Ang II in the SFO has been lacking. Here, implementing spatiotemporally restricted gene ablation by way of the Cre recombinase/loxP system, we provide the first direct evidence that the local RAS in the SFO has a critical role in blood pressure regulation. Using a transgenic mouse harboring an angiotensinogen (AGT) gene modified for Cre-mediated deletion (hAGT(flox)), in combination with gene transfer of an adenovirus encoding Cre targeted to the SFO, we show that deletion of the Ang II substrate in this brain region nearly abolishes the pressor and bradycardic effects of renin infused in the CNS. Immunohistochemical analyses verified intense and restricted expression of Cre in the SFO, which paralleled the decrease in AGT expression selectively in this site. Further physiological studies confirmed the integrity of central angiotensinergic and nonangiotensinergic cardiovascular response systems in the Cre-treated mice. In addition to establishing that AGT expression in the SFO and its local conversion to Ang II has a profound effect on blood pressure, this study provides proof-of-principle of the utility of this approach for dissecting the brain RAS and other complex systems in CNS cardiovascular circuits.

Genetic ablation of angiotensinogen in the subfornical organ of the brain prevents the central angiotensinergic pressor response. Publishing Authors By Initials

P Sinnayah,E Lazartigues,K Sakai,RV Sharma,CD Sigmund,RL Davisson,

For similar investigative techniques: genetic techniques: gene transfer techniques: transfection research abstracts see: investigative techniques: genetic techniques: gene transfer techniques: transfection research

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Genetic ablation of angiotensinogen in the subfornical organ of the brain prevents the central angiotensinergic pressor response. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Circulation research

VOLUME: 99

Page Numbers: 1125-31

Journal Abbreviation: Circ. Res.

ISSN: 1524-4571

DAY: 19

MONTH: 10

YEAR: 2006

Genetic ablation of angiotensinogen in the subfornical organ of the brain prevents the central angiotensinergic pressor response. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 47103

Genetic ablation of angiotensinogen in the subfornical organ of the brain prevents the central angiotensinergic pressor response. Keywords Mesh Terms:

KEYWORDS: Transfection

MESH TERMS: physiology

Chemical & Substance for Abstract: Genetic ablation of angiotensinogen in the subfornical organ of the brain prevents the central angiotensinergic pressor response. Information

Substance Name: Renin

Registry Number: EC 3.4.23.15

Grant and Affiliation Information for Genetic ablation of angiotensinogen in the subfornical organ of the brain prevents the central angiotensinergic pressor response.

AFFILIATION: Department of Anatomy and Cell Biology, Roy J. and Lucille A. Carver College of Medicine, the University of Iowa, Iowa City, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: HL63887

ACRONYM: HL

MEDLINETA: Circ Res

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