Adenovirus-mediated human prostasin gene delivery is linked to increased aldosterone production and hypertension in rats
Adenovirus-mediated human prostasin gene delivery is linked to increased aldosterone production and hypertension in rats
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DOI：
10.1152/ajpregu.00660.2002
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发表时间：
2003-04-01
影响因子：
2.8
通讯作者：
Chao, L
中科院分区：
文献类型：
--
作者：
Wang, C;Chao, J;Chao, L
前列腺素已被证明是培养的肾和支气管上皮细胞中上皮钠通道的激活剂。在这项研究中，我们评估了腺病毒介导的人前列腺素基因转移对 Wistar 大鼠血压调节和钠重吸收的影响。在大鼠肾上腺、肝脏、肾脏、心脏、肺和主动脉中鉴定出人前列腺素 mRNA 的表达，并在接受前列腺素基因转移的大鼠的循环和尿液中检测到免疫反应性人前列腺素。单次注射携带前列腺素基因的腺病毒会导致血压持续升高3-4周。血压升高伴随着血浆醛固酮水平升高和血浆肾素活性降低。血压和血浆醛固酮水平的升高以及血浆肾素活性的降低与人前列腺素转基因的表达相关。基因转移后3天，在发生高血压之前检测到血浆醛固酮水平升高，表明刺激盐皮质激素的产生是前列腺素的主要目标。前列腺素基因转移显着减少尿 K+ 排泄，但增加尿 Na+ 和激肽释放酶排泄。肾激肽释放酶水平升高可促进尿钠排泄，这可能导致钠逃逸并防止前列腺素基因转移后血压进一步升高。总之，这些结果表明前列腺素通过调节肾素-血管紧张素-醛固酮和激肽释放酶-激肽系统参与血压和电解质稳态。
Prostasin has been demonstrated to be an activator of epithelial sodium channels in cultured renal and bronchial epithelial cells. In this study, we evaluated the effects of adenovirus-mediated gene transfer of human prostasin on blood pressure regulation and sodium reabsorption in Wistar rats. Expression of human prostasin mRNA was identified in rat adrenal gland, liver, kidney, heart, lung, and aorta, and immunoreactive human prostasin was detected in the circulation and urine of rats receiving prostasin gene transfer. A single injection of adenovirus carrying the prostasin gene caused prolonged increases in blood pressure for 3-4 wk. Blood pressure increase was accompanied by elevated plasma aldosterone levels and reduced plasma renin activity. The increase in blood pressure and plasma aldosterone levels as well as the reduction of plasma renin activity correlated with the expression of human prostasin transgene. Elevated plasma aldosterone levels were detected at 3 days after gene transfer before the development of hypertension, indicating that stimulation of mineralocorticoid production is the primary target of prostasin. Prostasin gene transfer significantly reduced urinary K+ excretion but increased urinary Na+ and kallikrein excretion. Elevated renal kallikrein levels promote natriuresis, which may lead to sodium escape and prevent further increases of blood pressure after prostasin gene transfer. In summary, these results suggest that prostasin participates in blood pressure and electrolyte homeostasis by regulating the renin-angiotensin-aldosterone and kallikrein-kinin systems.