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

我们项目的最终目标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，我们使用从大鼠肾脏微解剖的每个肾单元段提取的总RNA进行逆转录聚合酶中国反应（RT-PCR），定位血管紧张素原、腺苷A_1受体和α _<1B>-肾上腺素能受体mRNA表达的管状分布。这些RT-PCR产物采用溴化乙啶染色和特异探针进行Southern杂交检测。近端小管和肾小球均可见血管紧张素原mRNA。此外，我们还发现了这些表达的生长依赖性降低（提交）。腺苷a1受体mRNA分布于肾小球、Henle髓质及皮质厚升袢、髓质及皮质集合小管及近端小管（Hypertension 26: 1181-1185,1995）。最后，我们显示了α _<1B>-肾上腺素能受体mRNA在肾小球、近端小管、肾髓和肾皮质袢的分布（肾Int.1997, in press）。在不久的将来，我们将对其他肾上腺素能受体如alpha_<1A>-、alpha_<1D>-、alpha_<2A>-、alpha_<2B>-、alpha_<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信息。

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.