权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Prostasin as a diagnositc and therapeutic target for salt-sensitive hypertension

前列腺素作为盐敏感性高血压的诊断和治疗靶点

基本信息

批准号：
17590834
负责人：
KITAMURA Kenichiro
金额：
$ 2.24万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590834/
关键词：
sodium channels serine protease prostasin hypertension

项目摘要

Generation of transgenic animal models for prostasinWe developec an adenoviral vector carrying human prostasin cDNA and injected into Wister rats. Rats expressing human prostasin gene showed high blood pressure and hyper aldosteronism. These phenotypes were abolished when the adrenal glands were removed prior to the virus injection, suggesting :hat adrenal gland is responsible for the prostasin mediated hyperaldosteronism.Application for the diagnosis of salt-sensitive hypertension in humansWe developed prostasin specific RIA system to elucidate the causative role of prostasin in the hypertension in humans. We measured urinary prostasin levels in 121 hypertensive patients and 26 healthy volunteers. We found that urinary prostasin levels had strong positive correlation with urinary aldosterone levels as well as with urinary Na/K ratio which is a marker for the activity of the epithelial sodium channels in the kidney. We also showed a positive correlation between urinary prostasin and plasma aldosterone levels.Taken together, these findings suggest that urinary prostasin levels might be a good marker for the ENaC activities in the renal tubules. Previously, we demonstrated that aldosterone induces urinary prostasin expression in primary aldosteronism patients. Our current research data indicate the important relationship between aldosterone and prostasin in general hypertensive population.

前列腺素转基因动物模型的建立我们构建了携带人前列腺素cDNA的腺病毒载体，并将其注射到Wister大鼠体内。表达人前列腺素基因的大鼠表现出高血压和高醛固酮血症。这些表型在病毒注射前去除肾上腺后消失，提示：前列腺素介导的醛固酮增多症是由肾上腺引起的。在盐敏感性高血压诊断中的应用我们建立了前列腺素特异性放射免疫分析系统，以阐明前列腺素在高血压中的致病作用。我们检测了121例高血压患者和26例健康志愿者的尿前列腺素水平。我们发现，尿前列腺素水平与尿醛固酮水平以及尿Na/K比值（肾脏上皮钠通道活性的标志物）呈强正相关。尿前列腺素水平与血浆醛固酮水平呈正相关，提示尿前列腺素水平可能是反映肾小管上皮细胞ENaC活性的良好指标。以前，我们证明了醛固酮诱导原发性醛固酮增多症患者尿前列腺素的表达。我们目前的研究资料表明，在一般高血压人群中，醛固酮和前列腺素之间存在着重要的关系。