angiotensin II-induced target organ damage in mice running title: Ang II infusion and ADMA

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