IL-6 deficiency protects against angiotensin II induced endothelial dysfunction and hypertrophy.
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).


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 mumol/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.
Schrader
Laura I
LI
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, USA.
Kinzenbaw
Dale A
DA
Johnson
Andrew W
AW
Faraci
Frank M
FM
Didion
Sean P
SP
D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006984:Hypertrophy; D015850:Interleukin-6 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D015850:Interleukin-6; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D014665:Vasodilator Agents; D013481:Superoxides; D000804:Angiotensin II; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D000109:Acetylcholine