Role of asymmetric dimethylarginine in inflammatory reactions by angiotensin II.

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(-6) 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).

Effect of fenofibrate on the level of asymmetric dimethylarginine in individuals with hypertriglyceridemia.

Objective: To test whether treatment with fenofibrate decreases asymmetric dimethylarginine (ADMA) level in hypertriglyceridemic individuals.

Methods: In the present study, 45 subjects with hypertriglyceridemia were recruited to receive treatment with fenofibrate (200 mg/d). Serum concentrations of ADMA, malondialdehyde (MDA), nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) were measured.

Fenofibrate decreases asymmetric dimethylarginine level in cultured endothelial cells by inhibiting NF-kappaB activity.

Previous investigations have demonstrated that endogenous inhibitors of nitric oxide synthase (NOS), such as asymmetric dimethylarginine (ADMA), contribute importantly to endothelial dysfunction, and that fenofibrate has a protective effect on the endothelium in rats treated with low-density lipoprotein (LDL) by reducing ADMA levels. In the present study, we explored further the possible mechanism underlying inhibition of ADMA generation by fenofibrate in cultured human umbilical vein endothelial cells (HUVECs). Endothelial injury was induced in cultured HUVECs by incubation with oxidative LDL (ox-LDL) and the levels of ADMA, lactate dehydrogenase (LDH), NO and tumour necrosis factor-alpha (TNF-alpha) in the conditioned medium were measured.