| Background and Objective: During the past years, many researches have been focused on NO for its critical role in the development of cardiovascular diseases. In our study, I/R injury was produced in rats with atherosclerosis. Some of the animals were treated with Simvastatin later to determine the impact of Simvastatin on the effect of NO and the expression of endothelial nitric oxide synthase and inducible nitric oxide synthase in coronary artery endothelia during the progression of I/R injury.Material and Methods: 100 healthy mature male Wistar rats were randomly divided into 5 groups. The first group was given normal food (normal food group, n=20). The second group was treated with high cholesterol diet (hyperchelosterolemia group,n=20). The third (Simvastatin treated group,n=20) was given high cholesterol diet, treated with Simvastatin at the dose of 5mg/kg.d since the 4th week. The fourth group (L-NAME treated group, n=20) fed on high chlesterol diet, provided with Simvastatin 5mg/kg.d and NG-niteo-L-Arginine-methyl-ester 10mg/kg.d since the 4th week. The fifth group was given high cholesterol diet and taken as sham operation group (Sham group, n=20).Normal food group, hyperchelosterolemia group, Simvastatin treated group and Simvastatin and L-NAME treated group were operated to develop I/R injury. The left coronary arteries of the animals were ligated to produce 30 min of ischemia, and 5 min, 20 min and 120 min of reperfusion respectively.Heart rate, serum nitric oxide, serum cholesterol and the expression of eNOS and iNOS in coronary artery endothelia of all animals were detected in the study.The variation of HR was detected. Blood samples were taken to test the level of serum NO before ischemia and at the times after 30 min of ischemia, 5 min, 20 min and 120 min ofreperfusion respectively. High-SABC immunohistochemistry analysis was performed to detect the expression of eNOS and iNOS in coronary artery endothelia. Electroscope was used to observe the alteration in structure of endothelia cell produced by cholesterol.Results: The treatment with both Simvastatin and L-NAME reduced HR. The serum cholesterol level of rats given high cholesterol diet was significantly higher than that of normal food group. However, Simvastatin treated group had the lower serum cholesterol level than hyperchelosterolemia group, which indicated that Simvastatin strongly down-regulated the serum cholesterol level. After 30 min of ischemia, serum NO, eNOS and iNOS of HC group were reduced. Hyperchelosterolemia might down-regulate the expression of eNOS and iNOS. After 5 min of reperfusion, iNOS of HC group increased. After 20min of reperfusion, the level of iNOS of HC group rose significantly, when eNOS and iNOS of SM group decreased. After 120min of reperfusion, serum NO, eNOS and iNOS of SM group were more than those of HC group. At any time, L-NAME inhibited the effect of Simvastatin on serum NO, eNOS and iNOS.The results implied that Simvastatin could reverse the changes induced by cholesterol and down-regulate the expression of iNOS in the early stage of reperfusion. During the advanced stage of reperfusion, serum NO, eNOS and iNOS could be increased significantly. The synthesis and release of NO play important roles in the process that Simvastatin counteracts atherosclerosis and I/R injury.The role of NO in I/R injury is still in hot debates. A lot of researches indicate that I/R injury decrease the NO synthesis in endothelia cells of coronary artery, while additional NO or its precursor could milden the damage in myocardium. Insteadly, some scholars reported that after 1/R injury, increased NO injured myocardium more severely, when inhibitors of NOS reduced the damage. NO may be a coin with two sides, but it is sure that modulating the density of active NO and the expression of eNOS and iNOS is very important to control cardiovascular diseases.
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