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Interleukin‐6‐Deficiency Protects Against Both Acute and Chronic Angiotensin II‐Induced Endothelial Dysfunction
Author(s) -
Didion Sean P,
Schrader Laura I,
Kinzenbaw Dale A,
Faraci Frank M
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a590-b
Subject(s) - endothelial dysfunction , angiotensin ii , endocrinology , medicine , oxidative stress , acetylcholine , endothelium , in vivo , renin–angiotensin system , superoxide , incubation , vasodilation , cytokine , blood pressure , chemistry , biology , enzyme , biochemistry , microbiology and biotechnology
The goal of this study was to test the hypothesis that IL‐6 mediates increases in blood pressure, vascular oxidative stress and endothelial dysfunction in response to angiotensin II (Ang II). Responses of carotid arteries from control and IL‐6‐deficient (IL‐6−/−) mice were examined following acute overnight incubation with Ang II (10 nmol/L) or chronic in vivo infusion of Ang II (1.4 mg/kg/d for 14 days). Baseline blood pressure and Ang II‐induced hypertension were similar (P>0.05) in control and IL‐6−/− mice. Acetylcholine produced concentration‐dependent relaxation that was similar (P>0.05) in vessels from vehicle‐infused control and vehicle‐infused IL‐6−/− mice. In contrast, Ang II‐infusion produced marked impairment of responses to ACh in carotid arteries from control, but not IL‐6−/− mice (eg, 100 μmol/L ACh produced 51±7 and 80±5% relaxation in vessels from Ang II‐infused control and IL‐6−/− mice, respectively). IL‐6‐deficiency also protected against endothelial dysfunction in response to acute Ang II treatment. Endothelial dysfunction could be reproduced in vessels from IL‐6−/− mice following overnight incubation with Ang II plus recombinant IL‐6 (0.1 nmol/L). Ang II‐induced increases in vascular superoxide levels were reduced in IL‐6−/− mice. These findings demonstrate that vascular expression of IL‐6 is essential for Ang II‐induced increases in superoxide and endothelial dysfunction.