| ObjectiveThe purpose of this study is to explore the effects of advanced glycation end-products AGEs and its receptor RAGE in hypertension arteries remodeling , and investigate the influence of telmisartan and pyridoxamine to vascular remodeling of spontaneously hypertensive rats (SHR) .MethodsForty-eight twenty-two-week-old male SHR were randomized into telmisartan treated group (T group, 6 mg·kg -1·d -1, n=12) ,pyridoxamine treated group (P group, 200mg·kg -1·d -1, n=12) , telmisartan and pyridoxamine treated group (T+P group, telmisartan 6 mg·kg -1·d -1 and pyridoxamine 200mg·kg -1·d -1,n=12) ,SHR distilled water control( HCgroup , 2 ml·d -1, n=12), while age and sex matched thirteen Wistar-Kyoto rats( NCgroup ,2 ml·d -1, n=13) were served as normal control,The former three groups were administered for 16 weeks by gavage in mixture with 2 ml distilled water,SHR and WKY control were given the same amount of distilled water.Systolic blood pressure was examined by the tail-cuff method by the BP-98AL instrument once two weeks .The Tw/Rl,W/L,percentages of media collagen ,and the ratio of elastin area/collagen area were detected by computer aided imaging system using slices of thoracic aorta hematoxylin-eosin,picric acid-picrosirius red , and victoria blue B-ponceau S double staining of elasticity fibrin and collagen fibrin 16 weeks later . The levels of serum AGEs and chymase in the aorta abdominalis were measurd by ELISA method;AngII contents in plasma and aorta abdominalis were determined by Radioimmunoassay ;The RAGE, ERK1 and ERK2 , in thoracic aorta were detected by immunohistochemical method ;immunity set turns the method examination chest aorta organization RAGE, ERK1 and ERK2;the expression of RAGE, ERK1, ERK2 , chymase , AT1 Ra and NADPH mRNA in the thoracic aorta were examined by quantitative real-time polymerase chain reaction ; Serum NO were examined by nitric reductive enzymatic, Serum NOS were tested by colorimetry, Serum SOD analysed by xanthine oxidase and MDA were tested by TBA .All statistics were analysed by SPSS version 16.0 software and the value of P<0.05 was considered statistical significant .Results1.The systolic blood pressure of T group and TP group were decreased significantly (P<0.05) compared with those which were not treated at the beginning of the experiment .2.Compared with HC group,the ratio of Tw/Rl, W/L, the percentages of media collagen of the thoracic aorta in P group, T group and TP group were decreased significantly(P < 0.05) while the ratio of elastic fiber /collagen fiber increased significantly (P<0.05)in the 3 groups .3. Compared with HC group,the serum AGEs decreased significantly (P<0.05)in P group, T group and TP group , among them TP groups was more obvious.4. Compared with NC group,the chymase in the aorta abdominalis in all SHR groups were increased but have no statistics meaning;(P>0.05); To compare with NC group, the Chymase mRNA in thoracic aorta in HC group, P group and TP group increased significantly(P<0.05), while it was similar between the T and NC group .5. Compared with NC group,the AngII in all SHR groups were increased significantly (P<0.05);Compared with HC group,T group,P group and TP group were obviously increased(P<0.05).6.Semi-quantitative immunohistochemistry results of RAGE:the levels of RAGE were increased in all SHR groups than NC group, while compared with HC group, T group,P group and TP group were decreased significantly(P<0.05); Compared with HC group, the RAGE mRNA of thoracic aorta in T group, P group and TP group decreased significantly(P<0.05), P group and TP group were more lower.7. Semi-quantitative immunohistochemistry results of ERK1 and ERK2 :the levels of ERK1 were increased significantly(P<0.05) in all SHR groups than NC group, while compared with HC group, T group,P group and TP group were decreased significantly(P<0.05);and TP group was lower than P group(P<0.05).Compared with HC group, the ERK1 and ERK2 mRNA of thoracic aorta were decreased significantly(P<0.05) in T group, P group and TP group .8. The SOD vitality and the levels of the serum NO were higher (P<0.05)in T group, P group and TP group,than HC group ;The SOD vitality in P group and TP group were higher than T group(P<0.05).Compared with HC group,the serum NOS in P group and TP group were increased significantly(P<0.05),while the serum MDA were decreased significantly in T group, P group and TP group(P<0.05).ConclusionWe found telmisartan may alleviate the Thoracic Aorta remodeling in spontaneously hypertension rats, in addition to it combined with AT1 R and anti the physiology characteristic of the AngII, it may decreased AGEs-RAGE level , reduced ERK 1/2 expressions, part's repressed oxidative stress.We also found pyridoxamine may alleviate the thoracic aorta remodeling in spontaneously hypertension rats,probably because it can lower AGEs level and repress oxidative stress.when telmisartan combinated with pyridoxamine may distinctly repress the vascular remodeling ,they can obviously improve the liver function and also significantly repressed the oxidative stress .
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