摘要
目的 观察波生坦对DOCA(脱氧皮质酮 ) 盐型高血压大鼠 (DHR)血压、血浆内皮素 1(ET 1)浓度和左心室内膜下心肌间微小血管密度的影响 ,探讨ET 1在其病理机制中的可能作用。方法 18只清洁级雄性SD大鼠 ,切除左侧肾脏后 1周 ,随机等分并制作为对照组、模型组和波生坦组 ,其中波生坦组给予波生坦 10 0mg/kg·d灌胃 ,每周各测血压 1次 ,4周末处死动物 ,采静脉血放免法测定血浆ET 1浓度 ,取左心室行免疫组化检测内膜下心肌间微小动脉和毛细血管密度。结果血压 :4周末模型组和波生坦组分别为 (180± 8)mmHg及 (16 2± 8)mmHg,较对照组 (12 2± 5 )mmHg明显升高 (P <0 0 5 ) ,而波生坦组则较模型组低 (P <0 0 5 ) ;血浆中ET 1浓度 :模型组和波生坦组较对照组ET 1血浆浓度高 (P <0 0 1) ,波生坦组较模型组高 (P <0 0 1) ;微小动脉密度 :模型组 (2 8 0 2±0 76 )mm-2 和波生坦组 (2 3.6 4± 0 82 )mm-2 分别比对照组 (16 .5± 0 88)mm-2 高 ,波生坦组较模型组低 (P <0 0 1) ,而毛细血管密度模型组 (182 3± 110 )mm-2 和波生坦组 (2 0 98± 134)mm-2 则分别比对照组 (2 4 5 0± 117)mm-2 低 ,波生坦组较模型组高 (P <0 0 1)。结论 波生坦能抑制DOCA 盐型高血压大鼠心内膜下微小动脉增多以及毛细血?
Objective To investigate the effect of a nonselective endothelin antagonist bosentan on the myocardial microvascular vessels in DOCA- Salt hypertensive rats. Methods Eighteen male Sprague-Dawley rat s were unilaterally nephrectomized, randomly divided into three groups. One gr oup served as controls, drinking tap water. Two groups were administered DOCA s ubcutaneously (50 mg/kg·week), and fed with 1% saline, receiving placebo or bos entan (100 mg/kg·d) for 4 weeks. Density of arterioles (<20 μm in lumen dia meter) were determined in the myocardium using immunolabelling with anti-smooth muscle α-actin antibody, and capillaries with an anti-laminin antibody. Results Systolic blood pressure was (122±5)\{mm Hg\} in unilaterall y nephrectomized rats (UniNx), (180±8)\{mm Hg\} in DOCA-salt (P<005 ve rsus UniNx), and (162±8) \{mm Hg\} in bosentan treated DOCA-salt (P<0 05 vs UniNx or DOCA- salt). Arteriolar and capillary densities were significan tly altered in subendocardial myocardium. Arteriolar density was (16.5±088)m m\+\{-2\} in UniNx, (2802±076)mm\+\{-2\} in DOCA-salt (P<001 versus UniNx ) and (23.64±082)mm\+\{-2\} in bosentan-treated DOVA-salt(P<00 1 versus UniNx or DOCA-salt). Capillary density per square millimetre was (2 450±117)\+\{-2\} in UniNx, (1 823±110)mm\+\{-2\} in DOCA-salt (P<001 versus UniNx ) a nd (2 098±134)mm\+\{-2\} in bosentan-treated DOCA-salt(P<001 versus Uni Nx or DOCA-salt). Conclusion In DOCA-salt hypertensive rats, bot h subendocardial arteriolar growth and capillary rarefaction were found in left ventricular myocardium, which were partially improved by ET-1 receptor antagonist. This finding suggests a role for endothelin-1 in cardiac arteriol ar growth and capillary rarefaction,which may have pathophysiological implications in myocardial ischemia in hyperte nsion.
出处
《高血压杂志》
CSCD
2004年第5期442-446,共5页
Chinese Journal of Hypertension
基金
江苏省教育厅自然科学研究基金项目 (Q2 12 3 0 3 1)
