| Cytological experiments demonstrate that physiological and elevated shear stress can inhibit the formation of atherosclerotic plaque by protecting endothelial cells, but oscillatory or lower shear stress may accelerate atherosclerosis by injurying endothelium function. In this study we first use Doppler ultrasound technique to measure shear stress in vivo and evaluate its effect on vascular remodeling in the procession of atherosclerosis.Objectives:1.To observe dynamic changes of shear stress in the procession of atherosclerosis. 2. To determine the degree of endothelial dysfunction at different stage of atherosclerosis. 3. To determine the relationship between shear stress and endothelium function > NO and ET-1 level. 4 To evaluate the effect of shear stress on the arterial intima-media thickness.Materials and methods:! 20 male big ear white rabbits were included in this study, weight 2.0 to 2.4kg, age 5 to 6 month, consecutively fed withmixture of 1% cholesterol, 2% yolk powder, 5% pork oil for 12 weeks. 2. Blood samples were obtained from ear veins to perform biochemical analysis at baseline, after feeding 2 weeks and after feeding 12 weeks. Biochemical parameters included serum total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol and triglycerides, nitric oxide and endothelin-1 level. Blood flow dynamic parameters included blood viscosity, red blood cell aggregation index, red blood cell transformation index and hemotocrit. 3. Doppler ultrasound was applied to measure endothelium-dependent dilation and endothelium-independent dilation in external iliac artery at different stage of atherosclerosis after the rabbits were anaesthesiaed. 4. Shear stress was calculated according to the following equation: T m = q *4Vm/Dr. 5. External iliac artery sample was cut off to manufacture tissue section after fed 12 weeks. Arterial intima-media thickness was measured under light microscope after being fixed and stained.Results: 1. After fed with high cholesterol diet for 2 weeks (HC, hypercholesterolemic stage), compared with baseline, the serum Teh, HDL, LDL, TG all increased significantly; the NO level decreased significantly (P<0.01), the ET-1 level showed no remarkable changes. After fed with high cholesterol diet for 12 weeks (AS, atherosclerosis stage), compared with HC stage, the serum Teh, HDL, LDL and TG increased markedly; the NO level decreased from 152.10?.37umol to 94.30?0.85umol (P<0.01), the ET-1 level increased from 195.20?.07umol to 271.90?2.42umol (P<0.01). 2. Compared with baseline, at HC stage red blood cell (RBC) transformation index decreased (P<0.01), blood viscosity elevated significantly (P<0.01), no significant changes were found in RBC aggregation index and hemotocrit (P>0.05). Compared with hypercholesterolemic stage, at AS stage RBCtransformation index, aggregation index and hemotocrit all decreased distinctively (P<0.01, P<0.01, P<0.01). 3. The EDO index was respectively 15.70 + 3.16%, 9.65 + 3.16% and 3.05?.23% at baseline, HC stage and AS stage. The EDD index at HC stage and AS stage was respectively much lower than that of baseline (P<0.01, P<0.01). 4. At HC stage, the EDD index and NO level decreased significantly, the injuried EDD index was positively correlated to NO level (r=0.88). At AS stage the EID was damaged to a great degree, the ET-1 level increased significantly, the injuried EID index was negtively correlated to ET-1 level (r= -0.86). 5. At AS stage, shear stress of external iliac artery decreased significantly (P<0.01), negative correlation was found between dropped shear stress and elevated ET-1 level (r= -0.86); Positive correlation was found between dropped shear stress and injuried EID index (r=0.78). 6. Intima-media thickness of external iliac artery was 342 ?1 urn, the average shear stress at AS stage was 9.48?.60 dynes/cm2, the IMT was negatively correlated to the lower shear stress (r= -0.75)Conclusions: 1. Long term high cholesterol diet can lead to vascular endothelium dysfunction, at HC stage EDD i...
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