Differential effects of AT1 receptor and Ca2+ channel blockade on atherosclerosis, inflammatory gene expression, and production of reactive oxygen species

  • Derek E. Doran
    Division of Cardiology, Department of Medicine, Emory University School of Medicine and the Atlanta VA Medical Center, Atlanta, GA, United States
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  • Daiana Weiss
    Division of Cardiology, Department of Medicine, Emory University School of Medicine and the Atlanta VA Medical Center, Atlanta, GA, United States
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  • Yong Zhang
    Division of Cardiology, Department of Medicine, Emory University School of Medicine and the Atlanta VA Medical Center, Atlanta, GA, United States
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  • Kathy K. Griendling
    Division of Cardiology, Department of Medicine, Emory University School of Medicine and the Atlanta VA Medical Center, Atlanta, GA, United States
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  • W. Robert Taylor
    Corresponding author at: Division of Cardiology, Emory University Hospital, Woodruff Memorial Research Building-Suite 319, 1639 Pierce Drive, Atlanta, GA 30322, United States. Tel.: +1 404 727 8921; fax: +1 404 727 3330.
    Division of Cardiology, Department of Medicine, Emory University School of Medicine and the Atlanta VA Medical Center, Atlanta, GA, United States
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      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.


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