Published online before print June 9, 2008, doi: 10.1161/HYPERTENSIONAHA.108.115402
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(Hypertension. 2008;52:205.)
© 2008 American Heart Association, Inc.
Editorial Commentaries |
The Flame That Lights the Fire
Oxidative Stress, Inflammation, and Renal Damage in Angiotensin II–Induced Hypertension
From the Hypertension and Vascular Research Unit, Lady Davis Institute for Medical Research and Department of Medicine, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
Correspondence to Ernesto L. Schiffrin, Lady Davis Institute for Medical Research and Department of Medicine, Sir Mortimer B. Davis-Jewish General Hospital, 3755 Côte Ste-Catherine Rd, #B-127, Montreal, Quebec, Canada H3T 1E2. E-mail ernesto.schiffrin@mcgill.ca
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Low-grade inflammation has acquired progressive recognition over the past few years as a mechanism for cardiovascular and renal damage. In hypertension, the activation of inflammatory mediators has been demonstrated in blood vessels, the heart, and the kidney in angiotensin (Ang) II–dependent models of hypertension, such as human angiotensinogen/human renin double transgenic rats1 and rats infused with Ang II,2 or in mineralocorticoid-induced hypertension.3
Both Ang II and endothelin-1 trigger an inflammatory process that participates in the mechanisms of hypertension. In a mouse model deficient in macrophages, the osteopetrotic mouse, Ang II- and endothelin-1–dependent hypertension were blunted together with oxidative stress generation, inflammatory mediator expression, vascular remodeling, and endothelial dysfunction.4,5 In human hypertension, inflammatory biomarkers, specifically C-reactive protein but also others, predict incident hypertension.6
Ang II exerts proinflammatory effects by stimulating redox-sensitive signaling cascades leading to mitogen-activated protein kinase activation, more specifically, p38 mitogen-activated protein kinase. Oxidative stress then stimulates inflammatory mediators, including nuclear factor 
B and activator protein-1. These, in turn, trigger production of chemokines, such as monocyte chemoattractant peptide-1, involved in macrophage recruitment, and activation of proinflammatory and prothrombotic agents, such as plasminogen activator inhibitor-1, and adhesion molecules, such as vascular cell adhesion molecule-1 and intercellular adhesion molecule-1.7 These inflammatory actions may require the participation of T-lymphocytes, important mediators in Ang II–induced hypertension. Guzik et al8 have shown that mice lacking T and B cells (RAG-1–/– mice) have blunted hypertension and do not develop abnormalities of vascular function during Ang II infusion or exposure to deoxycorticosterone acetate-salt, changes that are
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