ABSTRACT
Objective:To explore influence of monotherapy or combined use of telmisartan and pyridoxamine on aor-tic remodeling in spontaneously hypertensive rats (SHR)and its possible mechanism.Methods:A total of 48 male SHE were randomly and equally divided into hypertension control group,telmisartan group,group,and telmisartan+ group (combined treatment group). Kyoto Wistar rats of the same age and gender were regarded as normal blood pressure control group (normal control group). Thoracic aortic section were examined by related staining af-ter 16 weeks intervention to calculate the ratio of aortic wall thickness to radius of lumen (Tw/Rl),the ratio of wall area to lumen area (W/L),and the area ratio of media elastic fiber/collagen fiber. Concentrations of related en-zymes and receptor etc. of abdominal aortic were measured.Results:Compared with hypertension control group, there was significant rise in ratio of media elastic fiber/collagen fiber area and significant reduction in media collagen fiber/media area ratio in telmisartan group,pyridoxamine monotherapy group and combined treatment group,and there were significant decrease in Tw/Rl [(0.17±0.02)vs. (0.12±0.01)]and W/L [(0.29±0.03)vs. (0.22± 0.02)]ratios in combined treatment group,P <0.05 or <0.01;immunohistochemistry indicated that there were significant reductions in thoracic aortic receptor of advanced glycation end products (RAGE) [(0.24±0.03)vs.(0.17±0.03)]and extracellular signal-regulated kinase 1/2 (p-ERK1/2 )expression [(0.63 ± 0.06)vs. (0.37± 0.04)]in combined treatment group,P <0.05,<0.01. Fluorescence quantitative PCR indicated that medication can significantly reduce nicotinamide adenine dinucleotide phosphate (NADPH)oxidase subunit p47phox mRNA ex-pression (P <0.01 all),especially in combined treatment group (P =0.001).Conclusion:Combined use of telmis-artan and pyridoxamine is superior to the single use of either drug on improving thoracic aortic remodeling in SHR, the mechanism may be related to it reduces local expression of RAGE and p-ERK1/2 ,and inhibits oxidase subunit p47 of NADPH.
ABSTRACT
Objective To investigate the effects and the mechanism of telmisartan and pyridoxamine on oxidative stress in spontaneously hypertensive rats(SHR).Methods SHRs(male,20 weeks of age) were randomly divided into four groups (n＝ 12 for each):hypertension control (HC) group (2 ml of distilled water),telmisartan group[T,6 mg/(kg · d)],pyridoxamine group[P,200 mg/(kg · d)]and combined group(TP,6 mg/kg telmisartan and 200 mg/kg pyridoxamine per day).Treatments were continued for 16 weeks.The normal control group included 13 WKY rats and received gastric lavage with distilled water.SBP of tail artery was measured during the intervention ervey 2 weeks.The levels of AGEs,SOD and MDA were measured by ELISA,xanthine oxidase and thiobarbituric acid methods after the intervention.Expressiones of NF-κBp65,ERK1 and ERK2 in renal tissue were detected by immunohistochemistry.Expression of RAGE in the renal cortex was investigated by Western blot.Results SOD activity was decreased in the HC group.The levels of AGEs,MDA,RAGE and the activations of NF-κBp65 and ERK1/2 were increased in the HC group (t＝4.53,5.52,2.93,al1 P＜0.05).After the 16 weeks' intervention,SOD activity was elevated in T,P and TP groups compared to that in HC group (P＜0.05).The positive expressiones of NF-κBp65,ERK1 and ERK2 were significantly reduced in T,P and TP groups compared to those in HC group (F＝20.13、148.82、18.70,all P＜0.05).All the positive expressiones of NF-κBp65,ERK 1and ERK2 were lowest in the TP group versus T and P groups (t ＝ 3.58、2.84,P ＜ 0.05).Conclusions Telmisartan and pyridoxamine can alleviate the oxidative stress in spontaneously hypertensive rats,which may result from the blocking effect of Ang Ⅱ,the reduction of AGEs-RAGE and inhibiting the signal pathways of ROS,NF-κBp65 and ROS-ERK1/2.