内皮素-1前体基因反义寡核苷酸对正常和高血压大鼠血流动力学的影响

我们筛选出针对内皮素－１（ＥＴ－１）前体基因反义硫代寡核苷酸片断（ＥＴＡＳＯＤＮ）,已证明ＥＴＡＳＯＤＮ能显著抑制培养内皮细胞ＥＴ－１的生成,本应用该片断,对下沉和腹主动脉狭窄－高盐摄入型高血压大鼠侧脑室进行注射,记录注射前后血流动力学指标、注射后侧脑室周围组织中ＥＴ－１的含量及分布,ＥＴＡＳＯＤＮ对正常和高血压大鼠的影响,发现高血压大鼠脑干ＥＴ－１含量明显高于正常大鼠;ＥＴＡＳＯＤＮ能降低高血压

Effect of ET-1 antisense oligodeoxynucleotide on the hemodynamics of normal and experimental hypertensive rats

It was previously found that a phosphorothioated antisense oligodeoxynucleotide (ETASODN) significantly inhibits production of endothelin-1 (ET-1). The purpose of the present study was to determine whether intracerebroventricular injection of ETASODN targeted to prepro-ET-1 is capable of exerting the same preventing effect on the aorta narrowing of experimentally modeled hypertensive rats. Radioimmunoassay showed that ET-1 level in the brain stem of hypertensive rats was significantly elevated. In addition to down-regulating the ET-1 level, astisense could also reduce mean arterial pressure (MAP), heart rate and LVSP in model rats. The antisense also down-regulated the ET-1 level in hypothalamus and brain stem, reducing MAP in normal control rats. After treatment with the antisense, the value of delta MAP was markedly lowered in experimental hypertensive rats as compared to the control ones. Thus it appears that (1) ET-1 might play an important role in central cardiovascular regulation in rats and (2) antisense ETASODN might be used in treatment of hypertension via inhibiting ET-1 production.