Expression and localization of NK1R, substance P and CGRP are altered in dorsal root ganglia neurons of spontaneously hypertensive rats (SHR)
Expression and localization of NK1R, substance P and CGRP are altered in dorsal root ganglia neurons of spontaneously hypertensive rats (SHR)
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DOI：
10.1016/j.molbrainres.2005.03.015
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发表时间：
2005-07-29
期刊：
影响因子：
--
通讯作者：
Gontijo, JAR
中科院分区：
文献类型：
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作者：
Boer, PA;Ueno, M;Gontijo, JAR
肾脏在原发性高血压的发病机制中起着关键作用，因为肾脏血流动力学和/或肾小管水盐处理的原发缺陷导致液体和电解质滞留。以往的研究表明，在Wistar-京都大鼠(WKY)中，肾盆压力的增加增加了同侧肾传入神经活动(ARNA)、同侧肾盆P物质(SP)释放和对侧尿钠排泄。然而，自发性高血压大鼠(SHR)表现出肾反射活动受损，部分与肾盆感觉受体水平的外周缺陷有关。此外，肾盆腔给药不能使大多数自发性高血压大鼠的ARNA增加，其浓度可使WKY显著增加。我们观察了NK1受体(NK1R)、P物质和降钙素基因相关肽(CGRP)在7周龄和14周龄SHR不同背根节(DRG)细胞亚型和肾盆中的表达和定位。结果表明，与WKY大鼠相比，SHR大鼠背根神经节细胞中SP和CGRP的表达增加。此外，自发性高血压大鼠背根神经节细胞膜表面和肾盆中NK1R的表达呈进行性的、显著的、年龄依赖性的减少。综上所述，本研究结果提示，SOR大鼠肾脏感觉神经元激活受损可能与神经肽表达改变和/或DRG细胞NK1R表达减少有关。这种异常可能导致自发性高血压患者钠滞留增加和血压升高。(C)2005 Elsevier B.V.保留所有权利。
The kidneys play a pivotal role in the pathogenesis of essential hypertension because of a primary defect in renal hemodynamics and/or tubule hydro-saline handling that results in the retention of fluid and electrolytes. Previous studies have shown that increasing the renal pelvic pressure increased ipsilateral afferent renal nerve activity (ARNA), the ipsilateral renal pelvic release of substance P (SP) and the contralateral urinary sodium excretion in Wistar-Kyoto rats (WKy). However, spontaneously hypertensive rats (SHR) present an impaired renorenal reflex activity associated, partly, with a peripheral defect at the level of the sensory receptors in the renal pelvis. Furthermore, the renal pelvic administration of SP failed to increase ARNA in most of SHR at concentrations that produced marked increases in WKY. Since we have assessed the expression and localization of NK1 receptor (NK1R), SP and calcitonin gene-related peptide (CGRP) in different dorsal root ganglia (DRG) cell subtypes and renal pelvis of 7- and 14-week-old SHR. The results of this study show increased SP and CGRP expression in the dorsal ganglia root cells of SHR compared to WKy rats. Additionally, there was a progressive, significant, age-dependent, decrease in NK1R expression on the membrane surface in SHR DRG cells and in the renal pelvis. In conclusion, the results of the present study suggest that the impaired activation of renal sensory neurons in SUR may be related to changes in the expression of neuropeptides and/or to a decreased presence of NK1R in DRG cells. Such abnormalities could contribute to the enhanced sodium retention and elevation of blood pressure seen in SHR. (c) 2005 Elsevier B.V. All rights reserved.