Abstract:Aim To investigate the effects of activated renin angiotensin system in the vascular tissue on production of reactive oxygen species and nitric oxide.Methods Ten male Wuzhishan minipigs were divided into two groups,fed with normocholesterolemic(control;n=5) or hypercholesterolemic(2% cholesterol,hyperlipid,n=5) food for 3 months.Carotid arteries were isolated and the changes of TC,AngⅡ,ROS,NO and T-AOC of the vascular tissue were determined.In addition,hUVEC(human umbilical vein endothelial cell) were incubated with Ang I and chymostatin or with Ang I and losartan respectively for 24 h,the suspernatant was collected to measure the concentration of AngⅡ,ROS and NO. Results In comparison to the normocholesterolemic state,hypercholesterolemia led to a significant increase in TC content(108%±28%,p<0.01),AngⅡ generation (115%±20%,p<0.01) and ROS production(144%±28%,p<0.01),but it led to a significant decrease in NO(51%±5%,p<0.01) and T-AOC(56%±5%,p<0.01).Cultrured hUVEC could convert Ang I to AngⅡ.AngⅡ increased by11 times in the presence of 10 nmol/L Ang I as compared with control group,and the level of ROS also increased while NO decreased significantly.When hUVEC were incubated with Ang I plus 100 or 500 μmol/L chymostatin,AngⅡ generation was reduced by 61%±6% or 65%±7% respectively,and the ROS decreased while NO increased significantly as compared with only Ang I.When hUVEC were incubated with Ang I plus Losartan,the generation of ROS and No was almost the same as compared with control group on condition that AngⅡ generation was not reduced. Conclusion hypercholesterolemia could activate renin angiotensin system of the vascular tissue,which results in an increased vascular tissue production of ROS and a decreased NO.This effect might be mediated by AT1 receptor.