Aline Boer Patrícia, Ueno Mirian, Sant'ana Jenifer S M, Saad Mário J A, Gontijo José Antonio Rocha
Departamento de Clínica Médica, Faculdade de Ciências Médicas, Laboratório Balanço Hidro-Salino, Núcleo de Medicina e Cirurgia Experimental, Universidade Estadual de Campinas (UNICAMP), 13083-970 SP, Brazil.
Brain Res Mol Brain Res. 2005 Jul 29;138(1):35-44. doi: 10.1016/j.molbrainres.2005.03.015.
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 NK(1) receptor (NK(1)R), 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 NK(1)R 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 SHR may be related to changes in the expression of neuropeptides and/or to a decreased presence of NK(1)R in DRG cells. Such abnormalities could contribute to the enhanced sodium retention and elevation of blood pressure seen in SHR.
由于肾血流动力学和/或肾小管水盐处理的原发性缺陷导致液体和电解质潴留，肾脏在原发性高血压的发病机制中起关键作用。先前的研究表明，增加肾盂压力可增加Wistar - Kyoto大鼠（WKy）同侧肾传入神经活动（ARNA）、同侧肾盂P物质（SP）释放以及对侧尿钠排泄。然而，自发性高血压大鼠（SHR）存在肾肾反射活动受损，部分与肾盂感觉受体水平的外周缺陷有关。此外，在能使WKy大鼠显著增加ARNA的浓度下，向SHR大多数大鼠肾盂注射SP未能增加ARNA。因为我们已经评估了7周龄和14周龄SHR不同背根神经节（DRG）细胞亚型和肾盂中NK(1)受体（NK(1)R）、SP和降钙素基因相关肽（CGRP）的表达和定位。本研究结果显示，与WKy大鼠相比，SHR背根神经节细胞中SP和CGRP表达增加。此外，SHR DRG细胞和肾盂膜表面NK(1)R表达存在随年龄增长的、显著的、依赖性的下降。总之，本研究结果表明，SHR肾感觉神经元激活受损可能与神经肽表达变化和/或DRG细胞中NK(1)R表达减少有关。这些异常可能导致SHR钠潴留增强和血压升高。
