胖Zucker大鼠肠系膜动脉多巴胺D1受体介导的血管舒张功能受损及其机制  

Impaired dopamine D_1 receptor-mediated vasorelaxation of mesenteric arteries in obese Zucker rats and its underlying mechanisms

作　　者：符金娟[1] 韩愈[1] 王震[1] 关蔚蔚[1] 刘渔凯[1] 杨迪[1] 黄河飞[1] 杨素菲[1] 曾春雨[1] 周林[1] 

机构地区：[1]第三军医大学大坪医院野战外科研究所心血管病专科医院重庆市心血管病研究所,重庆400042

出　　处：《中华高血压杂志》2014年第10期940-944,共5页Chinese Journal of Hypertension

基　　金：国家杰出青年科学基金(30925018);国家自然科学基金(81070559,81270338)

摘　　要：目的观察多巴胺D1受体激动剂Fenoldopam介导的血管舒张反应性在胖、瘦Zucker大鼠中的差异。方法取12~14周健康雄性胖、瘦Zucker大鼠（n=12）,采用鼠尾动脉无创测压法测定血压;采用离体微血管张力测定系统,观察雄性胖、瘦Zucker大鼠肠系膜三级动脉在内皮完整与去除后,Fenoldopam（1×10-8~3×10-6 mol/L）对苯肾上腺素（PHE,1×10-5 mol/L）预收缩血管的舒张作用。用多巴胺D1受体拮抗剂SCH23390（10-7 mol/L）预孵育Zucker大鼠肠系膜动脉30min,观察Fenoldopam通过多巴胺D1受体舒张血管的特异性。采用蛋白免疫印迹法测定胖、瘦Zucker大鼠肠系膜组织多巴胺D1受体表达量的差异。结果与瘦Zucker大鼠相比,胖Zucker大鼠的血压增高。在Fenoldopam 3×10-6 mol/L时,瘦Zucker大鼠肠系膜动脉的舒张效应明显强于胖Zucker大鼠[（63.43±13.79）%比（20.75±8.60）%,P〈0.01]。去内皮前后,胖、瘦Zucker大鼠肠系膜动脉对Fenoldopam的舒张效应比较,差异无统计学意义（均P〉0.05）。SCH23390可以拮抗Fenoldopam对胖、瘦Zucker大鼠血管的舒张效应。蛋白免疫印迹结果显示,瘦Zucker大鼠肠系膜组织多巴胺D1受体表达量高于胖Zucker大鼠[（1.26±0.04）%比（0.74±0.06）%,P〈0.01]。结论与瘦Zucker大鼠相比,胖Zucker大鼠血压增高;增高的血压可能与肠系膜动脉多巴胺D1受体表达量下降引起的Fenoldopam的血管舒张效应下降有关。Objective To investigate the difference of dopamine D1receptor-mediated vasorelaxation of mesenteric arteries between obese and lean Zucker rats,as well as its underlying mechanisms. Methods The blood pressures of obese and lean Zucker rats（12-14weeks）were measured at tail artery（n=12）. In an in-vitro microvascular tension measurement system,the relaxation effect of Fenoldopam（1×10-8 to 3×10-6 mol/L）on mesenteric arteries from all rats,with or without intact endothelium,was evaluated in a setting of phenylephedrine（PHE,1×10-5 mol/L）pretreatment. Pre-incubated the mesenteric arteries with D1 receptor antagonist（SCH23390,1×10-7 mol/L）for30min to identify the specificity of D1receptor-mediated vasorelaxation. D1 receptor expression of mesenteric arteries was tested by Western blot. Result Compared with lean Zucker rats,obese rats showed higher blood pressure and had obviously lower vasorelaxation subjected to Fenoldopam at 3×10-6 mol/L [（63.43±13.79）% vs（20.75±8.60）%,P〈0.01]. Fenoldopam-induced vasorelaxation was endothelium-independent,as there was no different for this vasorelaxation in mesenteric arteries with or without intact endothelium（all P〉0.05）. Fenoldopam-induced vasorelaxation of all rats was blocked by SCH23390,which by itself had no effect on the mesenteric artery.Further,D1 receptor protein expression was found to be higher in the artery of lean Zucker rats than that of obese Zucker rats [（1.26±0.04）% vs（0.74±0.06）%,P〈0.01]. Conclusions Impaired dopamine D1 receptormediated vasorelaxation is observed in mesenteric artery of obese rather than lean Zucker rats,possibly due to the decreased expression of D1 receptor in resistance artery,which might be associated with high blood pressure in obese Zucker rats.

关 键 词：Zucker大鼠 多巴胺D1受体 肠系膜动脉 血管舒张 

分 类 号：R363[医药卫生—病理学]