The endogenous ouabain: Molecular basis of its role in hypertension and cardiovascular complications
The endogenous ouabain: Molecular basis of its role in hypertension and cardiovascular complications
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DOI：
10.2741/1711
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发表时间：
2005-09-01
影响因子：
3.1
通讯作者：
Bianchi, G
中科院分区：
文献类型：
--
作者：
Ferrandi, M;Manunta, P;Bianchi, G
内源性哇巴因 (EO) 是哇巴因的一种密切相关的异构体，其水平升高与大鼠和人类高血压以及相关的心血管并发症有关。 EO影响心血管系统的发病机制涉及肾Na/K-ATP酶的调节（与肾小管钠重吸收有关）以及信号转导途径的激活，促进生长相关基因的转录。大鼠和人类的实验和临床证据刺激了药理学研究，以开发能够拮抗 EO 介导的细胞和分子改变的新型抗高血压药物。其中，洋地黄毒甙元衍生物PST 2238因其在体内口服剂量为μg/kg/天时能够拮抗哇巴因引起的血压和器官肥大的作用而被选中。 PST 2238 的药理学选择性和安全性表明，该化合物可能有效治疗那些与 EO 产生增加相关的肾脏钠处理改变和心血管并发症的高血压。
Elevated levels of the endogenous ouabain ( EO), a closely related isomer of ouabain, are implicated in rat and human hypertension and in related cardiovascular complications. The pathogenetic mechanisms through which EO affects the cardiovascular system involve the modulation of the renal Na/K-ATPase, implicated in renal tubular sodium reabsorption, and the activation of signal transduction pathways, promoting the transcription of growth-related genes. Experimental and clinical evidence on rats and humans stimulated the pharmacological research for developing novel anti-hypertensive agents able to antagonize the cellular and molecular alterations mediated by EO. Among them, the digitoxigenin derivate, PST 2238, has been selected for its ability to antagonize the ouabain-induced effects on blood pressure and organ hypertrophy at oral doses of mu g/kg/day in vivo. The pharmacological selectivity and safety of PST 2238 suggests that the compound may be effective for the treatment of those forms of hypertension in which renal sodium handling alterations and cardiovascular complications are associated with increased production of EO.