Circulation. 2002;105:393-396
doi: 10.1161/hc0302.102618
doi: 10.1161/hc0302.102618
(Circulation. 2002;105:393.)
© 2002 American Heart Association, Inc.
Current Perspectives |
The AT1-Type Angiotensin Receptor in Oxidative Stress and Atherogenesis
Part I: Oxidative Stress and Atherogenesis
From Klinik und Poliklinik Innere Medizin III (G.N.), Universität des Saarlandes, Homburg/Saar, Germany; and the Department of Medicine (D.G.H.), Division of Cardiology, Medical School of Emory University, Atlanta, Ga.
Correspondence to Dr Georg Nickenig, Klinik und Poliklinik Innere Medizin III, Universität des Saarlandes, 66421 Homburg/Saar, Germany. E-mail nickenig@med-in.uni-sb.de
Key Words: angiotensin • oxygen • atherosclerosis • endothelium • growth substances
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Introduction |
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Angiotensin II, the principal effector of the renin angiotensin system, is a multifunctional peptide that modulates blood pressure, water and sodium homeostasis, neuronal function, and other neurohumoral systems.1–3 Initial research with angiotensin II focused on its role in the pathogenesis of hypertension; however, in the past decade, increasing evidence has accumulated to indicate that this octapeptide is involved in the development of atherosclerosis, myocardial infarction, vascular and myocardial remodeling, and congestive heart failure.4–7 The effects of angiotensin II are mediated by 2 plasma membrane receptors, referred to as the AT1 and AT2 subtypes.3,4 In adult tissues, the AT2 receptor is predominantly expressed in the brain and adrenals, with lower levels expressed elsewhere.8 AT2 receptor stimulation leads to vasodilatation and inhibition of vascular smooth muscle growth. During embryogenesis, the AT2 receptor is expressed in developing arteries, and seems to play a role in curbing vascular smooth muscle growth and guiding the ultimate thickness of the vascular wall.8,9 Although interesting and important roles of the AT2 receptor continue to be defined, most of the known functions of angiotensin II are related to AT1 receptor activation. AT1 receptors belong to the 7-membrane–domain superfamily of G-protein–coupled receptors and are expressed in vascular smooth muscle cells, heart, lung, brain, liver, kidney, and adrenal glands.3 AT1 receptors are coupled to a variety of intracellular signaling molecules, including the phospholipases A2, C, and D, adenylate cyclase, voltage-dependent Ca2+ channels, and to a variety of kinases involved in phosphorylation cascades.2–4 Depending on the cell and organ type,
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