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Molecular biological studies on renal tubular adrenergic receptors in patients with essential hypertension

原发性高血压患者肾小管肾上腺素能受体的分子生物学研究

基本信息

批准号：
05670956
负责人：
UMEMURA Satoshi
金额：
$ 1.47万
依托单位：
Yokohama City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1995
项目状态：
已结题

项目摘要

The final goal of our project is to clarify the role of the renal sympathetic nervous system in the pathogenesis of essential hypertension. At the first step, to clarify the distribution of the adrenergic receptor, we performed reverse transcription-polymerase chian reaction (RT-PCR) using total RNA extracted from each nephron segment microdissected from the rat kidney and localized the tubular distribution of mRNA expression of the angiotensinogen, adenosine A_1 receptor and alpha_<1B>-adrenergic receptor. The products of these RT-PCR were detected by ethidium bromide staining and Southern blott hybridization using specific probes for these genes.Angiotensinogen mRNA was found in the proximal tubules and glomerulus. As well, we found the growth dependent decrease of these expression (In submission).Adenosine A1-receptor mRNA was distributed at the glomerulus, medullary and cortical thick ascending loop of Henle, medullary and cortical collecting tubules and proximal tubules (Hypertension 26 : 1181-1185,1995). Finally, we have shown the distribution of alpha_<1B>-adrenergic receptor mRNA at the glomerulus, proximal tubules and medullary and cortical loop of Henle (Kidney Int.1997, in press).In the near future, we will perform similar studies on the other adrenergic receptors such as alpha_<1A>-, alpha_<1D>-, alpha_<2A>-, alpha_<2B>-, alpha_<2C>-, and beta-adrenergic receptors. These results give us important basic informations to evaluate the roles of renal sympathetic nervous system in essential hypertension.

本课题的最终目的是阐明肾交感神经系统在原发性高血压发病机制中的作用。第一步，为了明确肾上腺素能受体的分布，我们用逆转录-聚合酶链反应（RT-PCR）技术，从大鼠肾脏显微解剖的每个肾单位节段中提取总RNA，定位血管紧张素原、腺苷A_1受体和α-肾上腺素能受体mRNA表达的肾小管分布<1B>。RT-PCR产物经溴化乙锭染色和Southern印迹杂交检测，血管紧张素原mRNA在近曲小管和肾小球中表达。腺苷A1受体mRNA分布于肾小球、髓质和皮质的Henle氏粗升袢、髓质和皮质的集合小管和近端小管（Hypertension 26：1181- 1185，1995）。最后，我们已经显示了α-<1B>肾上腺素能受体mRNA在肾小球、近端小管、髓袢和皮质袢中的分布（Kidney Int.1997，in press），在不久的将来，我们将对其他肾上腺素能受体如α<1A>-<1D>、<2A>α<2B>_<2C>-和β-肾上腺素能受体进行类似的研究。这些结果为评价肾交感神经系统在原发性高血压中的作用提供了重要的基础资料。