Differential Effects of AT1 Receptor and Ca++ Channel Blockade on Atherosclerosis, Inflammatory Gene Expression, and Production of Reactive Oxygen Species

• Type of Material: Article
• Authors: Derek E. Doran, Emory University; Daiana Weiss, Emory University; Yong Zhang, Emory University; Kathy Griendling, Emory University; W Robert Taylor, Emory University
• Language: English
• Date: 2007-11
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2007, Elsevier
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.atherosclerosis.2006.11.030
• Title of Journal or Parent Work: Atherosclerosis
• ISSN: 0021-9150
• Volume: 195
• Issue: 1
• Start Page: 39
• End Page: 47
• Grant/Funding Information: This work was supported by NIH P01 HL58000, RO1 HL70531, R01 DK059499, VA Merit Funding and a grant from Astra Zeneca, Inc.
• Keywords: Atherosclerosis; angiotensin II; oxidative stress; vascular biology; angiotensin II receptor antagonists
• Research Categories: Health Sciences, General; Biology, General

Abstract

Angiotensin II receptor blockade has been shown to inhibit atherosclerosis in several different animal models. We sought to determine if this effect was the result of blood pressure reduction per se or a result of the anti-inflammatory effects of receptor blockade. ApoE-deficient mice were fed a high fat diet and treated with either an angiotensin II receptor antagonist, candesartan (0.5 mg/kg/day, SC) or a calcium channel blocker, amlodipine (7.5 mg/kg/day, mixed with food). Atherosclerotic lesion area, aortic inflammatory gene expression as well as aortic H2O2 and superoxide production were assayed. We found that candesartan but not amlodipine treatment dramatically attenuated the development of atherosclerosis despite a similar reduction in blood pressure. Similarly, candesartan treatment inhibited aortic expression of inflammatory genes and production of reactive oxygen species, effects not seen with amlodipine. These data demonstrate that angiotensin II receptor blockade inhibits atherosclerosis by reducing vascular oxidative stress and inflammatory gene production independent of blood pressure reduction.