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(Hypertension. 2009;54:619.)
© 2009 American Heart Association, Inc.

Original Articles

Endogenous Interleukin-10 Inhibits Angiotensin II–Induced Vascular Dysfunction

Sean P. Didion; Dale A. Kinzenbaw; Laura I. Schrader; Yi Chu; Frank M. Faraci

From the Departments of Internal Medicine (S.P.D., D.A.K., L.I.S., Y.C., F.M.F.) and Pharmacology (F.M.F.), Division of Cardiovascular Diseases, Carver College of Medicine, Cardiovascular Center, University of Iowa, Iowa City.

Correspondence to Frank M. Faraci, PhD, Department of Internal Medicine, Division of Cardiovascular Diseases, E318-2 GH, Carver College of Medicine, University of Iowa, Iowa City, IA 52242-1081. E-mail frank-faraci{at}uiowa.edu

Angiotensin II (Ang II) produces inflammation and endothelial dysfunction in blood vessels. We tested the hypothesis that interleukin 10 (IL-10), an antiinflammatory cytokine, protects against Ang II–induced vascular dysfunction. Responses of carotid arteries from wild-type and IL-10–deficient mice (IL-10^–/–) were examined in vitro after overnight incubation with vehicle or Ang II (1 nmol/L). In arteries from wild-type mice, acetylcholine (an endothelium-dependent agonist) produced relaxation that was not affected by Ang II. In contrast, relaxation to acetylcholine in arteries from IL-10^–/– mice was reduced by >50% by Ang II (P<0.05) and this effect was prevented by a scavenger of superoxide. Vascular superoxide increased 2-fold (P<0.05) after treatment with Ang II in IL-10^–/– mice but not in wild-type. After systemic administration of Ang II (1.4 mg/kg per day for 10 days), Ang II produced modest impairment of endothelial function in wild-type mice but marked impairment in IL-10^–/– mice (P<0.05) that was reversed by a superoxide scavenger. Increases in arterial pressure in response to Ang II were similar in wild-type and IL-10^–/– mice. These findings provide the first evidence that endogenous IL-10 limits Ang II-mediated oxidative stress and vascular dysfunction both in vitro and in vivo suggesting that at least some of the protective effects of IL-10 may occur within the vessel wall.

Key Words: carotid artery • oxidative stress • inflammation • endothelium • genetically-altered mice