Cardiovascular Division, Department of Physiology, Universidade Federal de São Paulo, Escola Paulista de Medicina, Brazil.
Department of Morphology, Health Sciences Center, Universidade Federal do Espírito Santo, Brazil.
Brain Res. 2018 Nov 1;1698:43-53. doi: 10.1016/j.brainres.2018.06.025. Epub 2018 Jun 20.
The role of spinal cord neurons in renal sympathoexcitation remains unclear in renovascular hypertension, represented by the 2-kidney, 1-clip (2K1C) model. Thus, we aimed to assess the influence of spinal glutamatergic and AT1 angiotensin II receptors on renal sympathetic nerve activity (rSNA) in 2K1C Wistar rats. Hypertension was induced by clipping the renal artery with a silver clip. After six weeks, a catheter (PE-10) was inserted into the subarachnoid space and advanced to the T10-11 vertebral level in urethane-anaesthetized rats. The effects of intrathecally (i.t.) injected kynurenic acid (KYN) or losartan (Los) on blood pressure (BP) and rSNA were analysed over 2 consecutive hours. KYN induced a significantly larger drop in rSNA among 2K1C rats than among control (CTL) rats (CTL vs. 2K1C: -8 ± 3 vs. -52 ± 9 spikes/s after 120'). Los also evoked a significantly larger drop in rSNA among 2K1C rats than among CTL rats starting at 80' after administration (CTL vs. 2K1C - 80 min: -10 ± 2 vs. -32 ± 6; 100 min: -15 ± 4 vs. -37 ± 9; 120 min: -12 ± 5 vs. -37 ± 8 spikes/s). KYN decreased BP similarly in the CTL and 2K1C groups; however, Los significantly decreased BP in the 2K1C group only. We found upregulation of AT1 gene expression in the T11-12 spinal segments in the 2K1C group but no change in gene expression for AT2 or ionotropic glutamate (NMDA, kainate and AMPA) receptors. Thus, our data show that spinal ionotropic glutamatergic and AT1 receptors contribute to increased rSNA in the 2K1C model, leading to the maintenance of hypertension; however, the participation of spinal AT1 receptors seems to be especially important in the establishment of sympathoexcitation in this model. The origins of those projections, i.e., the brain areas involved in establishing the activity of spinal glutamatergic and angiotensinergic pathways, remain unclear.
脊髓神经元在肾交感神经兴奋中的作用在肾血管性高血压中仍不清楚，2 肾 1 夹（2K1C）模型就是一个代表。因此，我们旨在评估脊髓谷氨酸能和 AT1 血管紧张素 II 受体对 2K1C 大鼠肾交感神经活动（rSNA）的影响。通过用银夹夹闭肾动脉来诱导高血压。六周后，在乌拉坦麻醉的大鼠中，将导管（PE-10）插入蛛网膜下腔并推进至 T10-11 椎骨水平。分析鞘内（i.t.）注射犬尿氨酸（KYN）或氯沙坦（Los）对血压（BP）和 rSNA 的影响，共持续 2 小时。与对照组（CTL）大鼠相比，KYN 在 2K1C 大鼠中引起的 rSNA 下降幅度明显更大（CTL 与 2K1C：120'后分别为-8±3 和-52±9 个脉冲/s）。与 CTL 大鼠相比，Los 给药后 80'开始时也引起 rSNA 明显更大的下降（CTL 与 2K1C：-80' min：-10±2 与-32±6；100' min：-15±4 与-37±9；120' min：-12±5 与-37±8 个脉冲/s）。KYN 在 CTL 和 2K1C 组中的 BP 降低情况相似；然而，Los 仅在 2K1C 组中显著降低 BP。我们发现 2K1C 组 T11-12 脊髓节段的 AT1 基因表达上调，但 AT2 或离子型谷氨酸（NMDA、海人藻酸和 AMPA）受体的基因表达没有变化。因此，我们的数据表明，脊髓离子型谷氨酸能和 AT1 受体有助于 2K1C 模型中 rSNA 的增加，从而维持高血压；然而，在该模型中，脊髓 AT1 受体的参与似乎尤其重要。这些投射的起源，即涉及建立脊髓谷氨酸能和血管紧张素能途径活动的脑区，仍不清楚。
