The aim of the present study was to investigate the role of the endogenous nitric oxide synthase inhibitor asymmetrical dimethylarginine (ADMA) and its degrading enzyme dimethylarginine dimethylaminohydrolase (DDAH) in angiotensin II (Ang II) induced hypertension and target organ damage in mice. Mice transgenic for the human DDAH1 gene (TG) and wildtype (WT) mice (each n=28) were treated with Ang II 1.0µg/kg/min, Ang II 3.0µg/kg/min or phosphate buffered saline (PBS) over 4 weeks via osmotic minipumps. Blood pressure as measured by tail-cuff was elevated to the same degree in TG and WT mice. Plasma levels of ADMA were lower in TG than WT, and were not affected after 4 weeks by either dose of Ang II in both TG and WT animals. Oxidative stress within the wall of the aorta, measured by fluorescence microscopy using the dye dihydroethidium, was significantly reduced in TG mice. Ang II-induced glomerulosclerosis was similar between WT and TG mice whereas renal interstitial fibrosis was significantly reduced in TG compared to WT animals. Renal mRNA expression of PRMT1 and DDAH2 increased during infusion of Ang II whereas PRMT3 and endogenous mouse DDAH1 expression remained unaltered. Chronic infusion of Ang II in mice has no effect on plasma levels of ADMA after 4 weeks. However, overexpression of DDAH1 alleviates Ang II induced renal interstitial fibrosis and vascular oxidative stress, suggesting a blood pressure-independent effect of ADMA on Ang II induced target organ damage.