Bosentan对DOCA-盐敏感型高血压大鼠血管重构的影响

The Influence of Bosentan on Vascular Remodling in DOCASALT-RAT

目的 :观察Bosentan对DOCA -盐敏感型高血压大鼠血管重构的影响 ,探讨其血管重构的机制。方法 : 4 0只 16 0～ 180 g的雄性SD大鼠 ,切除左侧肾脏 ,一周后随机分为 4组。 1组为空白对照组 ,饮自来水。术后一周 ,2、3、4组予脱氧皮质酮 (DOCA)皮下注射 ,5 0mg/kg/w ,饮 1%盐水 ;在开始DOCA上皮下注射的同时 ,予药物灌胃 ,2组 :安慰剂 :3组 :Bosentan 10 0mg/kg/d ;4组 ;依那普利 2 0mg/kg/d ,持续 4周。每周测尾动脉压。 4周后 ,抽血并处死动物取材 ,放免法测内皮素 (ET)、血浆肾素活性 (PRA)。光镜下观察主动脉组织学改变 ,测主动脉厚度、直径。结果 :血压 :2周后 ,2～ 4组血压轻度升高 ,与对照组相比 ,P <0 .0 5 ;4周后 ,Bosentan可以减缓血压上升幅度。血浆ET浓度 :安慰剂组、依那普利组、对照组差别无显著性 :Bosentan组与对照组比显著升高 (P <0 .0 1) ;血浆PRA浓度 :对照组比其他 3组显著增高 ,差异显著 (P <0 .0 1) ;依那普利组比安慰剂组更低 ,差异显著 (P <0 .0 1) ;血管厚度 :安慰剂组、依那普利组显著高于对照组 (P <0 .0 5 ) ;Bosentan组与对照组于显著差异 ,明显低于安慰剂组 (P <0 .0 1) ;依那普利组与安慰剂组差别无显著性 ,(P >0 .0 5 )。结论 :Bosentan可延缓DOCA

Objective To investigate the effect of bosentan on remodling in aorta in DOCA_Salt_rat.Methods 40male sprague_dawley rats were unilaterally nephrectomized,survived 40rats were randomly divided into 4groups. One group served as controls,drinking tap water,three other groups were administered DOCA subcutaneously(50mg/kg/week)and 1%saline was added to their tap water for drinking. Simutanously,they were given placibo,bosentan 100g/kg/day,enalapril 20mg/kg/day.BP was measured using tail_cuff methods every week.After 4weeks treatment,blood were extacted from heart. plasma endothelin(ET).pre_renin_activity(PRA)were measured radiommunoasay.Histologic study of the aorta was examined using light microscope.Results BP treatment with DOCA and salt for 2 weeks led to a mild but significant hypertension;in placebo treated doca_rats,systolic blood pressure increased markly after 4 weeks.adminitration of bosentan blunted BP increasing.Plasma ET:no difference Plasma ET level was found Daily among control group,placebo group and enalapril group,incresing in bosentan group.PRA in rats treated with DOCASALT decended.Enalapril group vs placebo group ( P <0.05).Widths:aorta widths were increasing in placebo group and enalapril group. Bosentan can blunt remodling of aorta.Conclusion Bosentan can blunt BP increasing and aorta remodling.