30 May 2007
Previous investigations have demonstrated that angiotensin (Ang) II induces inflammatory reactions and asymmetric dimethylarginine (ADMA), an endogenous NOS inhibitor, might be a novel inflammatory factor. Endothelial cell activation was induced by incubation with Ang II or ADMA. Incubation with Ang II (10<sup>–6</sup> M) for 24 h elevated the levels of ADMA and decreased the levels of nitrite/nitrate concomitantly with a significant increase in the expression of protein arginine methyltransferase and a decrease in the activity of dimethylarginine dimethylaminohydrolase (DDAH). Exposure to Ang II (10<sup>–6</sup> M for 24 h) also enhanced intracellular ROS elaboration and the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-8, upregulated chemokine receptor CXCR<sub>2</sub> mRNA expression, increased adhesion of endothelial cells to monocytes and induced a significant increase in the activity of nuclear factor (NF)-ĸB, which was attenuated by pretreatment with the Ang II receptor blocker losartan (1, 3 and 10 µ M). Exogenous ADMA (30 µ M) also increased ROS generation and the levels of TNF-α and IL-8, decreased the levels of nitrite/nitrate, upregulated CXCR<sub>2</sub> gene expression, increased endothelial cell binding with monocytes and activated the NF-ĸB pathway, which was inhibited by pretreatment with losartan or L-arginine. These data suggest that ADMA is a potential proinflammatory factor and may be involved in the inflammatory reaction induced by Ang II.