Phillips M I, Wielbo D, Gyurko R
Department of Physiology, College of Medicine, University of Florida, Gainesville.
Kidney Int. 1994 Dec;46(6):1554-6. doi: 10.1038/ki.1994.444.
There are several ways of experimentally studying the influence of candidate genes on hypertension. The approach proposed here is antisense inhibition with antisense oligodeoxynucleotides (AS-ODNs) constructed to the 5' region of known sequences of angiotensinogen mRNA and angiotensin II type-1 receptor mRNA. The AS-ODNs were applied in vivo and in vitro. In vivo, direct injection of 50 micrograms of AS-ODN into the lateral ventricles of SHR reduced hypertension significantly (P < 0.01). There was no effect of AS-ODN i.c.v. in normotensive WKY rats. The phosphorothiated AS-ODN to the AT1 receptor mRNA also produced a long-lasting decrease in blood pressure in SHR (7 days). After AS-ODN treatment AT1 receptors were reduced in the PVN and anterior third ventricle area and Ang II levels were reduced in the brainstem. The results show the in vivo feasibility of using antisense inhibition of renin-angiotensin mRNA to reduce hypertension.
有几种通过实验研究候选基因对高血压影响的方法。这里提出的方法是用针对血管紧张素原mRNA和血管紧张素II 1型受体mRNA已知序列5'区域构建的反义寡脱氧核苷酸（AS - ODNs）进行反义抑制。AS - ODNs在体内和体外均有应用。在体内，向自发性高血压大鼠（SHR）侧脑室直接注射50微克AS - ODN可显著降低高血压（P < 0.01）。向正常血压的WKY大鼠脑室内注射AS - ODN没有效果。针对AT1受体mRNA的硫代磷酸化AS - ODN也使SHR的血压产生了持久下降（7天）。AS - ODN处理后，室旁核（PVN）和第三脑室前部区域的AT1受体减少，脑干中的血管紧张素II水平降低。结果表明，利用反义抑制肾素 - 血管紧张素mRNA来降低高血压在体内是可行的。
