| Objective:To establish an atherosclerotic rats model,the influence of vascular reactivity by a novel angiotensinⅡtype 1 receptor antagonist, olmesartan medoxomil, and the comparison of olmesartan medoxomil and candesartan cilexetil in endothelium protection was investigated in atherosclerotic rats. Moreover,to observe the level of NO,ET-1 and to discuss the mechanism of this action.Method:Forty male wistar rats that were randomly divided into four groups(A,B,C,D):control group, AS model group, candesartan cilexetil-treated group and olmesartan medoxomil-treated group,the rats were fed eight weeks all together.①The measuration of body weight and lipid levels in plasma:rats were weighed at 0,2,4,6and 8week respectively; Blood was collected and lipid levels in plasma were detected with chemical method in each group.②The evaluation of vascular reactivity:Thoracic aorta was prepared for vascular ring in each group at the end of 8 week,the rings were suspended in organ chambers,bathed in vessel buffering solution at 37℃, the artery was contracted with noradrenaline (10-6mol/L),the relaxation reactivity of rings to Acetylcholine(Ach) and Sodium Nitroprusside(SNP)(10-9,10-8,10-7,10-6,10-5mol/L) was detected respectively, to express vascular reactivity by means of concentration-response curve, Emax and IC50.③The measuration of NO and ET-1:Blood was collected in each group,NO was measured with chemical enzyme method,ET-1 was measured with radio-immunity method.Result:①The effect of olmesartan medoxomil to AS model rats on body weight and lipid levels in plasma:At 0 week,body weight and lipid levels in plasma were similar and there were no significance between each group (P>0.05);at the end of 8 week, body weight and lipid levels in plasma in AS rats were significantly greater than A group (P<0.01), olmesartan medoxomil and candesartan cilexetil-treated AS rats have no effect on body weight and lipid levels in plasmawas (P>0.05).②The effect of olmesartan medoxomil on vascular reactivity:the relaxation response to SNP in the aortic annulus of rats had no difference between each group(P>0.05).AS rats significantly shifted the concentration-response curve to the left, Emax and IC50 were statistical significance compared with A group (P<0.01).C and D group shifted the concentration-response curve to the right,the Emax of C group was 59.684±2.425%and IC50 was (9.71±0.992)×10-8mol/L, the Emax of D group was 63.629±2.165%and IC50 was (6.743±0.564)×10-8mol/L,these datas were significant difference compared with B group (P<0.01),meanwhile there was statistical significance between C and D group (P<0.05).③The effect of olmesartan medoxomil to AS rats on the level of NO and ET-l:At 0 week,there were no difference in each group (P>0.05);At the end of 8 week,the level of NO in A group rats was 36.987±3.051 umol/L and ET-1 was 31.966±3.523pg/ml, there were notable difference compared with AS Rats (P<0.01),the level of NO in D group was 29.94±3.807 umol/L and was higher than C group (P<0.05), whereas the level of ET-1 in D group was 58.261±5.137pg/ml and was lower than C group (P<0.05)Conclusion:①AS rats decrease endothelium-dependent relaxation obviously,whereas have no effection on endothelium-independent relaxation.②Olmesartan medoxomil and candesartan cilexetil can improve AS rats endothelium-dependent relaxation,furthermore the action of olmesartan medoxomil was much powerful than candesartan cilexetil.③The mechanism of olmesartan medoxomil on vascular reactivity is likely to increase the level of NO and decrease the level of ET-1. Objective:hs-CRP serum level and the CD40 mRNA expression of aorta in atherosclerotic(AS) rats were measured in this experiment.To observe the effect of anti-inflammatory on AS rats treated with olmesartan medoxomil, and further to compare the effect between olmesartan medoxomil and candesartan cilexetil.Methods:forty male Wistar rats were randomly divided into four groups:A control group, B AS model group, C candesartan cilexetil-treated group, D olmesartan medoxomil-treated group.B,C and D groups reproduced AS model,C and D group while giving candesartan cilexetil and olmesartan medoxomil to intervene respectively.①2ml of blood was collected at 0 week and the end of 8 week,then centrifuged and the supernatant was obtained,hs-CRP serum level was detecteded with enzyme-linked immunosorbent assay(ELISA),to investigate and compare hs-CRP serum level in each group.②To separated the thoracic aorta and abdominal aorta of rats quickly, the expression of CD40 of aorta in every group was detected by reverse transcript polymerse chain reaction (RT-PCR),and finally to take pictures and observe with UV detector.meanwhile with GADPH as an internal reference agent and conclude the relative expression level of CD40 in aortic tissue,to compare the expression of CD40 in rats aortic among the groups.Results:①At 0 week,the levels of serum hs-CRP were similar among the four groups and showed no significant difference(P>0.05);At the end of 8 weeek,the level of serum hs-CRP in AS rats were significantly higher than that in control group rats (P<0.01),among the two treated groups and no treated group, hs-CRP serum level was reduced obviously in two treated groups (P<0.01),furthermore the level of serum hs-CRP in olmesartan medoxomil-treated group was much lower than candesartan cilexetil (P<0.01).②The expression level of CD40 in AS rats aorta was obviously higher than control group (P<0.01),but compared with B group, CD40 mRNA expression in aorta of olmesartan medoxomil and candesartan cilexetil-treated rats decresed significantly (P<0.01),the level expression of CD40 in D group was lower than C group and the difference had statistically significant (P<0.01).Conclusion:①The level of serum inflammatory likeas hs-CRP was increased in AS rats,and expressed high level of CD40 in AS rats aorta.②Olmesartan medoxomil and candesartan cilexetil can reduce AS rats hs-CRP serum level and decrease the expression level of CD40 in aorta. Both of olmesartan medoxomil and candesartan cilexetil have the effect of anti-inflammatory to AS rats.③Compared with candesartan cilexetil-treated, the level of serum hs-CRP and the expression of CD40 decrease in olmesartan medoxomil-treated AS rats,therefore olmesartan medoxomil has a stronger anti-inflammatory effects on AS rats.
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