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.