南方医科大学学报

南方医科大学学报 ›› 2006, Vol. 26 ›› Issue (09): 1297-1300.

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内皮素及其受体在哇巴因高血压鼠发病机制中的作用

姜馨； 郭宁； 吕卓人；   

  1. 西安交通大学第一医院老年心血管内科； 西安交通大学第一医院老年心血管内科 陕西西安710061； 陕西西安710061；
  • 出版日期:2006-09-20 发布日期:2006-09-20
  • 基金资助:
    陕西省自然科学基础研究计划(2005C242)~~

Contribution of endothelin and its receptors to ouabain-induced hypertension in rats

JIANG Xin, GUO Ning, L? Zhuo-ren, Department of Geriatric Cardiology, First Hospital of Xi’an Jiaotong University, Xi’an 710061, China   

  1. 西安交通大学第一医院老年心血管内科； 西安交通大学第一医院老年心血管内科 陕西西安710061； 陕西西安710061；
  • Online:2006-09-20 Published:2006-09-20

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摘要： 目的探索内皮素及其受体在大鼠哇巴因高血压发病机制中的作用。方法雄性SD大鼠随机分为哇巴因组和生理盐水对照组,分别给予哇巴因或生理盐水腹腔注射6周,每周测量收缩压。分别于实验2、4、6周放免法测定血浆及心脏组织中内皮素的含量,实时荧光定量RT-PCR法检测大鼠左心室内皮素A、B两种受体mRNA水平,并用免疫组化法检测左心室内皮素A、B两种受体蛋白的表达。结果大鼠腹腔注射哇巴因4周后收缩压开始上升,6周后哇巴因组大鼠血压与对照组相比有显著性差异(P<0.001)。大鼠腹腔注射哇巴因2周后,血浆及心脏组织内皮素水平升高(P<0.01),左心室内皮素A型受体mRNA水平升高。4周时A型受体mRNA水平进一步升高且A型受体蛋白表达也增强,而B型受体mRNA及蛋白的表达在整个实验过程中均无显著变化。结论哇巴因高血压鼠血压升高前即出现血浆及心脏组织中内皮素含量增加,左心室内皮素A型受体转录及表达增强,提示内皮素可能通过其A型受体参与了哇巴因引起的血压升高及靶器官损害。 

Abstract: Objective To investigate the effect of endothelin and its receptors on ouabain-induced hypertension in rats. Methods Male Sprague-Dawley (SD) rats were treated with ouabain or saline for 6 weeks and their systolic blood pressure (SBP) were recorded weekly. At the end of 2, 4 and 6 weeks, respectively, the plasma and left ventricle endothelin contents were measured by radio-immunoassay, and real-time quantitative RT-PCR was employed to determine the mRNA level of endothelin type A receptor (ETAR) and type B receptor (ETBR) in the left ventricle, and the protein expressions of ETAR and ETBR were examined by immuno-histochemistry. Results After 4 weeks of intraperitoneal ouabain injection, the mean SBP in ouabain group increased till reaching a level significantly higher than that in the control group after 6 weeks (P<0.001). The plasma and left ventricle endothelin contents were significantly increased after 2 weeks of ouabain injection (P<0.01), and similarly, increased ETAR mRNA was observed. After 4 weeks of treatment, ETAR mRNA was increased continuously and the protein expression of ETAR upregulated in ouabain group as compared with the control group. The transcription and protein expression of ETBR were not altered by ouabain treatment. Conclusion Before detectable blood pressure elevation occurs, endothelin concentration and ETAR can be already upregulated in ouabain-induced hypertensive rats, suggesting that endothelin might be involved in the cardiovascular effects of ouabain via an action on ETAR. 

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