| PART1 Endothelial dysfunction in hypercholesterolemic rabbits and the interventional effects of polygonum cuspidatum sieb. et Zucc. and L-arginine.PART 2 Change of the DDAH activity in hypercholesterolemic rabbits and interventional effects of polygonum cuspidatum sieb. et Zucc.PART3 Interventional effect of polydatin on the vascular endothelial function in ADMA treated healthy rabbits' aorta strips.BACKGROUND :Hypercholesterolemia causes the endothelial dysfunction and atherosclerosis. Endothelial dysfunction is the pivotal mechanism of atherosclerosis. In this process, the disorder of nitric oxide synthase (NOS) plays a key role. Endogenous NOS inhibitor—asymmetric dimethylarginine (ADMA) increases significantly in atherosclerosis. It is considered a novel marker for atherosclerosis.OBJECTIVES:The objectives of this study are to explore the effects of ADMA and disordered NOS on endothelial dysfunction in vitro and in vivo,to understand the mechanism of endothelial dysfunction in atherosclerosis rabbits,and to investigate the possible mechanism of polygonum cuspidatum sieb. et Zucc.(HZ) and polydatin (PD) intervening in endothelial dysfunction and atherosclerosis. METHODS: 1. 36 Japanese rabbits were randomized into 6 groups. Except the control group(group NC),all the rest 5 groups were given cholesterol 1.5 g/day,lard 7.5 g/day and yolk powder 3 g/day. Among those five groups,four were feeding with polygonum cuspidatum sieb. et Zucc. 1 g/day(group SHZ),3 g/day (group MHZ),9 g/day (group LHZ) or L-arginine 4.2188 g/day (group Arg) separately. The fifth group was onlygiven high cholesterol diet (group HC). The feeding periods were 14 weeks. 2. The following contents were surveyed: A. EDD and NEDD of external iliac artery in vivo (measured with high-resolution ultrasound),serum lipids,NO,NOS(chemical method),plasma ET(RIA),ADMA,symmetric dime- thylarginine (SDMA) and L-arginine (aminoacid analyzer),the area of AS plaque in thoracic aorta (dyeing with Sudan Ⅳ),the degree of AS lesion in abdominal and external iliac arteries ,NOS activity on the wall of the abdominal artery (dyeing with NBT),the expression of iNOS mRNA and eNOS mRNA on the wall of the abdominal artery(in situ hybridation)and the contractive and dilatant functions of abdominal and external iliac arteries in vitro；B. the activities of dimethylarginine dimethylaminohydrolase (DDAH) in kidney (including the establishment of the determining method). 3. In the third part of the study, normal aorta strips were used. The following were surveyed: their response to using ADMA alone, influence of treating with ADMA ,intervention of polydatin (PD),influence of using ADMA and PD together on Emax and Kd that were contracted by PE.RESULTS:1. The results of vascular endothelial function in vivo,pathological changes ,vascular contractive and dilative functions in vitro were asfollows:A. EDD of external iliac arteries measured with high-resolution ultrasound was damaged after 1 week of atherogenic diet ,much earlier than NEDD,which was damaged after 6 weeks of atherogenic diet；serum lipids in group HC were much higher than those in group NC (especially TC and LDL),the level of serum NO,plasma ET and the activity of NOS were elevated significantly in group HC,so was the level of plasma ADMA. Contrasted with that in group NC,AS lesion in abdominal and external iliac arteries in group HC was much more serious ,dyeing of NOS on the medial layer of the artery wall was much darker, the expression of iNOS mRNA was much stronger ,and that of eNOS mRNA was on the contrary . The dilatant functions of abdominal and external iliac arteries to achetylcholine (Ach) were damaged significantly, but the contractive reaction to PE and the dilatant reaction to sodium nitroprusside (SNP) were not altered. Artery's IC50 to the dilatant reaction of SNP was much bigger in group HC. B. HZ could ameliorate vascular endothelial dysfunction caused by atheroge...
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