Published Online
on December 24, 2007

A more recent version of this article appeared on February 1, 2008

This Article Full Text (PDF) Data Supplement All Versions of this Article: 51/2/218    most recent HYPERTENSIONAHA.107.095885v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Weiss, D. Articles by Taylor, W. R. Search for Related Content PubMed PubMed Citation Articles by Weiss, D. Articles by Taylor, W. R. Related Collections Pathophysiology Mechanism of atherosclerosis/growth factors Related Article

Submitted on June 6, 2007
Revised on June 20, 2007

Deoxycorticosterone Acetate Salt Hypertension in Apolipoprotein E^-/- Mice Results in Accelerated Atherosclerosis. The Role of Angiotensin II

Daiana Weiss and W. Robert Taylor^*

From the Division of Cardiology, Department of Medicine (D.W., W.R.T.), and Wallace H. Coulter Department of Biomedical Engineering (W.R.T.), Emory University School of Medicine, Atlanta, Ga; and the Atlanta Veterans' Affairs Medical Center (W.R.T.), Decatur, Ga

^* To whom correspondence should be addressed. E-mail: wtaylor{at}emory.edu.

Abstract—Previous studies have shown that administration of angiotensin II to atherosclerosis-prone animal models results in an increase in the extent of atherosclerosis and that this effect may be independent of changes in blood pressure. We sought to determine whether atherosclerosis was increased in the setting of a low renin model of hypertension. Apolipoprotein E–deficient mice were made hypertensive using the deoxycorticosterone acetate salt model. We found that this resulted in a dramatic increase in the atherosclerotic lesion area in the setting of either a low- or high-fat diet. In the hypertensive animals, we observed an increase in angiotensin II staining that was localized to the adventitial macrophages. The increase in atherosclerosis was inhibited by administration of an angiotensin receptor antagonist, an angiotensin-converting enzyme inhibitor, or a renin inhibitor. In addition, blood pressure reduction, with either a calcium channel blocker or hydralazine, reduced the extent of atherosclerosis indicating an important contribution of the mechanical effects of elevated blood pressure. These data suggest that, even in the setting of hypertension that is not associated with activation of the systemic renin-angiotensin system, local generation of angiotensin II within the arterial wall may be of pathophysiological relevance to the development of atherosclerosis.

Key words: atherosclerosis • hypertension • angiotensin • renin • oxidative stress

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Cornelius F.H. Mueller and Georg Nickenig
Hypertension 2008 51: 175-176. [Extract] [Full Text] [PDF]

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