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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:2576.)
© 2007 American Heart Association, Inc.

Vascular Biology

IL-6 Deficiency Protects Against Angiotensin II–Induced Endothelial Dysfunction and Hypertrophy

Laura I. Schrader; Dale A. Kinzenbaw; Andrew W. Johnson; Frank M. Faraci; Sean P. Didion

From the Departments of Internal Medicine and Pharmacology, Cardiovascular Center, The University of Iowa Carver College of Medicine, Iowa City.

Correspondence to Sean P. Didion, PhD, Department of Internal Medicine, Division of Cardiovascular Medicine, 340-G Eckstein Medical Research Building, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242. E-mail sean-didion{at}uiowa.edu

Objective— The goal of this study was to test the hypothesis that IL-6 mediates the increases in superoxide, vascular hypertrophy, and endothelial dysfunction in response to angiotensin II (Ang II).

Methods and Results— Responses of carotid arteries from control and IL-6–deficient mice were examined after acute (22-hour) incubation with Ang II (10 nmol/L) or chronic infusion of Ang II (1.4 mg/kg/d for 14 days). The hypertrophic response and endothelial dysfunction produced by Ang II infusion was markedly less in carotid arteries from IL-6–deficient mice than that in control mice. IL-6 deficiency also protected against endothelial dysfunction in response to acute (local) Ang II treatment (eg, 100 µmol/L acetylcholine produced 100±4 and 98±4% relaxation in vehicle-treated and 51±4 and 99±4% relaxation in Ang II–treated, control, and IL-6–deficient vessels, respectively). Endothelial dysfunction could be reproduced in vessels from IL-6–deficient mice with combined Ang II plus IL-6 (0.1 nmol/L) treatment. Increases in vascular superoxide and IL-6, as well as reductions in endothelial nitric oxide synthase mRNA expression, produced by Ang II were absent in IL-6–deficient mice.

Conclusions— These data demonstrate that IL-6 is essential for Ang II–induced increases in superoxide, endothelial dysfunction, and vascular hypertrophy.

The role of IL-6 in endothelial dysfunction and oxidative stress produced by angiotensin II was investigated. IL-6 deficiency was associated with reductions in angiotensin II–induced endothelial dysfunction, vascular hypertrophy, and superoxide. Thus, IL-6 produced locally, within the vessel wall, contributes substantially to the vascular dysfunction produced by angiotensin II.

Key Words: genetically-altered mice • inflammation • oxidative stress • endothelium-dependent responses

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