IngentaConnect Effect of Olmesartan Medoxomil on Atherosclerosis: Clinical Impli...

Abstract:

Angiotensin II is a potent vasoconstrictor and may also contribute to the progression of atherosclerosis. In atheromatous lesions located in human coronary and carotid arteries, angiotensin-converting enzyme and angiotensin II levels are significantly increased. Angiotensin II is known to have proinflammatory actions in vascular tissues, inducing inflammatory cytokines and oxidative stress. In particular, angiotensin II activates the potent cytoplasmic transcription factor nuclear factor-κB, which regulates leukocyte adhesion molecules, tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1, and interleukin (IL)-6, and contributes to the recruitment of circulating mononuclear leukocytes to the arterial intima. Olmesartan medoxomil has one of the highest degrees of antihypertensive efficacy among the angiotensin II type 1 receptor antagonists. In the EUTOPIA (EUropean Trial on Olmesartan and Pravastatin in Inflammation and Atherosclerosis) trial, olmesartan medoxomil significantly reduced serum levels of high-sensitivity C-reactive protein, high-sensitivity TNFα, IL-6, and MCP-1, all of which are involved in promoting atherosclerosis. In a monkey atherosclerotic model, a 3-D intravascular ultrasound analysis of aortas showed that serum levels of MCP-1 and the degree of intimal hyperplasia were significantly lower after treatment with olmesartan medoxomil than before treatment. In VIOS (Vascular Improvement with Olmesartan Medoxomil Study), treatment with olmesartan medoxomil for 1 year, significantly reduced the wall-to-lumen ratio in arteries, whereas atenolol did not. Thus, olmesartan medoxomil, which rapidly reduces inflammatory markers, may have a beneficial antiatherosclerotic effect.

Keywords: Angiotensin II 1 receptor antagonists; Atherosclerosis; Olmesartan medoxomil

Document Type: Research article

Affiliations: 1: Department of Pharmacology, Osaka Medical College, Osaka, Japan

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Effect of Olmesartan Medoxomil on Atherosclerosis: Clinical Implications of the Emerging Evidence