Endogenous interleukin-10 inhibits angiotensin II-induced vascular dysfunction.
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 approximately 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.
Didion
Sean P
SP
Department of Internal Medicine, Division of Cardiovascular Diseases, Carver College of Medicine, University of Iowa, Iowa City, IA 52242-1081, USA.
Kinzenbaw
Dale A
DA
Schrader
Laura I
LI
Chu
Yi
Y
Faraci
Frank M
FM
D000109:Acetylcholine / Q000494:pharmacology; D000809:Angiotensins / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D051546:Cyclooxygenase 2 / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D011092:Polyethylene Glycols / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D000809:Angiotensins; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D013481:Superoxides; D016753:Interleukin-10; D011092:Polyethylene Glycols; D052247:Nitric Oxide Synthase Type II; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D013482:Superoxide Dismutase; C063471:polyethylene glycol-superoxide dismutase; D000109:Acetylcholine