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

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c DNA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为高血压和高醛固酮增多症。当注射病毒前摘除肾上腺时，这些表型被取消，这表明：肾上腺负责前列腺素介导的醛固酮增多症。应用于人类盐敏感型高血压的诊断我们建立了前列腺素特异性RIA体系，以阐明前列腺素在人类高血压中的致病作用。我们测定了121例高血压患者和26名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钠/钾比值呈显著正相关，尿钠/钾比值是反映肾脏上皮钠通道活性的指标。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ENaC活性的良好指标。在此之前，我们已经证实，在原发性醛固酮增多症患者中，醛固酮可以诱导尿前列腺素的表达。我们目前的研究数据表明，在普通高血压人群中，醛固酮和前列腺素之间存在重要的关系。

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.