Acute endotoxemia in rats induces down-regulation of V2 vasopressin receptors and aquaporin-2 content in the kidney medulla
Acute endotoxemia in rats induces down-regulation of V2 vasopressin receptors and aquaporin-2 content in the kidney medulla
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DOI：
10.1111/j.1523-1755.2004.00378.x
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发表时间：
2004-01-01
影响因子：
19.6
通讯作者：
Aguilera, G
中科院分区：
文献类型：
--
作者：
Grinevich, V;Knepper, MA;Aguilera, G
背景尽管血浆加压素（VP）水平不变或升高，但内毒素血症可导致液体代谢改变，表明肾脏对肽的作用不敏感。为了验证这一假设，我们检测了脂多糖（LPS）注射对肾脏V2受体和水通道蛋白-2表达的影响。血浆VP和尿渗透压，[H-3] VP与肾膜的结合，免疫印迹，水通道蛋白-2的免疫组化分析，V2 VP受体和细胞因子mRNA的原位杂交在腹腔注射LPS（250 μ g/100 g）后3 - 24小时测定。LPS注射引起尿渗透压的长期降低（长达24小时），而血浆钠或VP水平无显著变化。这与肾脏中V2 VP受体mRNA和VP受体数量的显著减少有关，这在LPS注射后长达12小时内是明显的。肾内髓质水通道蛋白-2也减少约50%。LPS刺激3 h后，肾髓质IL-1 β表达增加，6 h达高峰，12 h后开始下降，而IL-6 mRNA表达仅在3 h后才显著增加。对照组大鼠肾组织无白细胞介素mRNA表达。在体外孵育肾髓质切片与IL-1 β减少VP结合。对急性内毒素血症的炎症反应下调肾脏内髓质的V2 VP受体和水通道蛋白-2，导致肾脏浓缩尿液的能力长期受损。
Background. Endotoxemia can lead to fluid metabolism alterations despite unchanged or elevated plasma vasopressin (VP) levels, suggesting a refractoriness of the kidney to the effect of the peptide. To test this hypothesis, we examined the effect of lipopolysaccharide (LPS) injection on the expression of V2 receptors and aquaporin-2 in the kidney.Methods. Plasma VP and urine osmolality, and binding of [H-3] VP to kidney membranes, Western blot, and immunohistochemical analysis of aquaporin-2, in situ hybridization for V2 VP receptors and cytokines mRNAs were measured in the kidney 3 to 24 hours after LPS injection, 250 mug/100 g, intraperitoneally.Results. LPS injection caused prolonged decreases in urine osmolality (up to 24 hours) without significant changes in plasma levels of sodium or VP. This was associated with marked decreases in V2 VP receptor mRNA and VP receptor number in the kidney, which were evident for up to 12 hours after LPS injection. Aquaporin-2 in kidney inner medulla was also reduced by about 50%. LPS induced interleukin (IL)-1beta in the kidney medulla by 3 hours, reached maximum at 6 hours, and started to decline by 12 hours, while it increased IL-6 mRNA significantly only at 3 hours. Interleukin mRNA expression was absent in kidneys of control rats. In vitro incubation of kidney medulla slices with IL-1beta reduced VP binding.Conclusion. The inflammatory response to acute endotoxemia down regulates V2 VP receptors and aquaporin-2 of the kidney inner medulla resulting in prolonged impairment of the renal capacity to concentrate urine.