Potentiation of the antihypertensive action of losartan by peripheral overexpression of the ANG II type 2 receptor.

Potentiation of the antihypertensive action of losartan by peripheral overexpression of the ANG II type 2 receptor. Research Abstract Details 

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Potentiation of the antihypertensive action of losartan by peripheral overexpression of the ANG II type 2 receptor. Abstract Text:

Hongwei Li,Yongxin Gao,Justin L Grobe,Mohan K Raizada,Michael J Katovich,Colin Sumners,

Our previous studies demonstrated that peripheral overexpression of angiotensin II (ANG II) type 2 receptors (AT(2)R) prevents hypertension-induced cardiac hypertrophy and remodeling without altering high blood pressure. This, coupled with the observations that AT(2)R play a role in the antihypertensive actions of ANG II type 1 receptor (AT(1)R) blockers (ARBs), led us to propose that peripheral overexpression of AT(2)R would improve the antihypertensive action of losartan (Los) in Sprague-Dawley (SD) rats made hypertensive via chronic infusion of ANG II. Here we utilized adenoviral vector-mediated AT(2)R gene transfer to test this hypothesis. A single intracardiac injection of adenoviral vector containing genomic AT(2)R (G-AT(2)R) DNA and enhanced green fluorescent protein (EGFP) gene controlled by cytomegalovirus (CMV) promoters (Ad-G-AT(2)R-EGFP; 5 x 10(9) infectious units) into adult SD rats produced robust AT(2)R overexpression in cardiovascular tissues (kidney, lung, heart, aorta, mesenteric artery, and renal artery) that persisted for 3-5 days postinjection. By 7 days post viral injection, the overexpressed AT(2)R are reduced toward basal values in certain tissues (lung, kidney, and heart) and are undetectable in others (kidney and blood vessels). In two separate protocols, we demonstrated that the hypotensive effect of Los (0.125, 0.5, and 1.0 mg/kg iv) was significantly greater in the AT(2)R-overexpressing animals (-40.7 +/- 4.3, -41.8 +/- 4.8, and -48.1 +/- 2.6 mmHg, respectively) compared with control vector (Ad-CMV-EGFP)-treated rats (-12.4 +/- 2.2, -20.2 +/- 3.4, and -27.3 +/- 3.4 mmHg, respectively). These results provide support for a depressor role of AT(2)R and the proposal that combined AT(2)R agonist and ARB treatment may be an improved therapeutic strategy for controlling hypertension.

Potentiation of the antihypertensive action of losartan by peripheral overexpression of the ANG II type 2 receptor. Publishing Authors By Initials

H Li,Y Gao,JL Grobe,MK Raizada,MJ Katovich,C Sumners,

For similar genetic processes: gene expression regulation: up-regulation research abstracts see: genetic processes: gene expression regulation: up-regulation research

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Potentiation of the antihypertensive action of losartan by peripheral overexpression of the ANG II type 2 receptor. Journal Published:

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

Journal: American journal of physiology. Heart and circulat

VOLUME: 292

Page Numbers: H727-35

Journal Abbreviation: Am. J. Physiol. Heart Circ. Ph

ISSN: 0363-6135

DAY: 3

MONTH: 11

YEAR: 2006

Potentiation of the antihypertensive action of losartan by peripheral overexpression of the ANG II type 2 receptor. Information

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LANGUAGE: eng

NlmUniqueID: 100901228

Potentiation of the antihypertensive action of losartan by peripheral overexpression of the ANG II type 2 receptor. Keywords Mesh Terms:

KEYWORDS: Up-Regulation

MESH TERMS: genetics

Chemical & Substance for Abstract: Potentiation of the antihypertensive action of losartan by peripheral overexpression of the ANG II type 2 receptor. Information

Substance Name: PD 123319

Registry Number: 130663-39-7

Grant and Affiliation Information for Potentiation of the antihypertensive action of losartan by peripheral overexpression of the ANG II type 2 receptor.

AFFILIATION: Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL 32610-0274, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: HL-068085

ACRONYM: HL

MEDLINETA: Am J Physiol Heart Circ Physio

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