Interleukin‐10 Protects Against Angiotensin II‐Induced Oxidative Stress and Endothelial Dysfunction

Angiotensin II (Ang II) produces inflammation, oxidative stress and endothelial dysfunction in blood vessels. The goal of the present study was to test the hypothesis that interleukin 10 (IL‐10), a potent anti‐inflammatory 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 following overnight incubation with either vehicle or a low concentration of 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 markedly and selectively reduced by treatment with Ang II (e.g., 100 μmol/L acetylcholine produced 82±8 and 37±5% relaxation in vehicle‐ and Ang II‐treated arteries, respectively). This effect of Ang II in IL‐10 −/ − mice were reversed by PEG‐SOD (300 U/ml). Superoxide levels increased in aorta following treatment with Ang II in IL‐10 −/− mice but not in wild‐type. Following systemic administration of Ang II (1000 ng/kg/min or vehicle for 10 days via osmotic minipump), Ang II produced modest impairment of endothelial function in arteries from wild‐type mice but marked impairment in IL‐10 −/− mice (e.g., 100 μmol/L acetylcholine produced 102±3 and 55±1% relaxation in vehicle‐ and Ang II‐treated mice, respectively). Baseline levels and increases in arterial pressure in response to Ang II were similar in wild‐type and IL‐10 −/− mice. These findings provide the first direct evidence that IL‐10 limits Ang II‐mediated oxidative stress and impairment of endothelial function. This effect occurs both in vitro and in vivo suggesting that protective effects of IL‐10 may occur within the vessel wall.