Effects of long-term ouabain treatment on blood pressure, sodium excretion, and renal dopamine D1 receptor levels in rats
Effects of long-term ouabain treatment on blood pressure, sodium excretion, and renal dopamine D1 receptor levels in rats
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DOI：
10.1007/s00360-009-0391-z
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发表时间：
2010-01-01
期刊：
影响因子：
--
通讯作者：
Ren, Yanping
中科院分区：
文献类型：
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作者：
Zhang, Yurong;Yuan, Zuyi;Ren, Yanping
为了检测长期哇巴因治疗对血压（BP）、钠排泄和肾脏多巴胺D-1受体水平的影响，雄性Sprague-Dawley（SD）大鼠腹腔注射哇巴因（27.8 μ g kg（-1）d（-1））5周，每周记录收缩压（SBP）。5周后，测定钠排泄和多巴胺D-1受体激动剂非诺多泮介导的尿钠排泄，并通过Western印迹分析证实肾皮质多巴胺D-1受体的表达和磷酸化水平。用比色法测定哇巴因对非诺多泮抑制人近端肾小管上皮细胞（HK-2细胞）Na+-K+-ATP酶活性的影响。5周后，哇巴因组大鼠收缩压明显高于对照组（P < 0.01），但尿钠排泄量和肾皮质D-1受体表达水平降低，D-1受体磷酸化水平升高。静脉注射非诺多泮会导致对照大鼠的钠排泄增加，但未能诱导哇巴因治疗大鼠的尿钠排泄。非诺多泮对HK-2细胞Na+-K+-ATP酶活性有剂量-效应关系（10（-9）~ 10（-6）M），但纳摩尔浓度哇巴因预处理5天后，这种抑制作用明显减弱（P < 0.01）。我们建议，哇巴因诱导的肾脏多巴胺D-1受体功能的减少作为一种机制，负责钠潴留，这有助于高血压引起的慢性哇巴因治疗。
To examine the effects of chronic ouabain treatment on blood pressure (BP), sodium excretion, and renal dopamine D-1 receptor level, male Sprague-Dawley (SD) rats were treated with ouabain (27.8 mu g kg(-1) d(-1)) intraperitoneally for 5 weeks, and systolic blood pressure (SBP) were recorded weekly. After 5 weeks, sodium excretion and dopamine D-1 receptor agonist fenoldopam-mediated natriuresis were measured, and the expression and phosphorylation levels of the renal cortical dopamine D-1 receptor were confirmed by Western blot analysis. The effects of ouabain on fenoldopam-mediated inhibition of Na+-K+-ATPase activity were determined by colorimetric assays in human proximal tubular epithelial cells (HK-2 cells). After 5 weeks, the SBP in ouabain group was significantly higher than that in the control group (P < 0.01), but the sodium excretion and renal cortical D-1 receptor expression levels were reduced, and D-1 receptor phosphorylation levels were increased after ouabain treatment. Intravenous administration of fenoldopam caused an increased sodium excretion in control rats, but failed to induce natriuresis in ouabain-treated rats. In addition, fenoldopam induced a dose-respone (10(-9) to 10(-6) M) inhibition of Na+-K+-ATPase activity in HK-2 cells,but these effects were significantly diminished in HK-2 cells pretreated with nanomolar concentration of ouabain for 5 days (P < 0.01). We propose that the ouabain-induced reduction of the renal dopamine D-1 receptor function serves as a mechanism responsible for sodium retention, and this contributes to the hypertension induced by chronic ouabain treatment.