We demonstrated earlier that renal afferent pathways combine very likely “classical” neural signal transduction to the central nervous system and a substance P (SP)–dependent mechanism to control sympathetic activity. SP content of afferent sensory neurons is known to mediate neurogenic inflammation upon release. We tested the hypothesis that alterations in SP-dependent mechanisms of renal innervation contribute to experimental nephritis. Nephritis was induced by OX-7 antibodies in rats, 6 days later instrumented for recording of blood pressure (BP), heart rate (HR), drug administration, and intrarenal administration (IRA) of the TRPV1 agonist capsaicin to stimulate afferent renal nerve pathways containing SP and electrodes for renal sympathetic nerve activity (RSNA). The presence of the SP receptor NK-1 on renal immune cells was assessed by FACS. IRA capsaicin decreased RSNA from 62.4 ± 5.1 to 21.6 ± 1.5 mV s (*p < 0.05) in controls, a response impaired in nephritis. Suppressed RSNA transiently but completely recovered after systemic administration of a neurokinin 1 (NK1-R) blocker. NK-1 receptors occurred mainly on CD11⁺ dendritic cells (DCs). An enhanced frequency of CD11c⁺NK1R⁺ cell, NK-1 receptor⁺ macrophages, and DCs was assessed in nephritis. Administration of the NK-1R antagonist aprepitant during nephritis reduced CD11c⁺NK1R⁺ cells, macrophage infiltration, renal expression of chemokines, and markers of sclerosis. Hence, SP promoted renal inflammation by weakening sympathoinhibitory mechanisms, while at the same time, substance SP released intrarenally from afferent nerve fibers aggravated immunological processes i.e. by the recruitment of DCs.

我们之前证明，肾传入通路很可能结合了到中枢神经系统的“经典”神经信号转导和 P 物质 (SP) 依赖机制来控制交感神经活动。已知传入感觉神经元的 SP 含量在释放时介导神经源性炎症。我们测试了肾脏神经支配的 SP 依赖性机制的改变导致实验性肾炎的假设。大鼠的 OX-7 抗体诱导肾炎，6 天后记录血压 (BP)、心率 (HR)、药物给药和肾内给药 (IRA) 的 TRPV1 激动剂辣椒素以刺激传入肾神经通路包含 SP 和用于肾交感神经活动 (RSNA) 的电极。通过 FACS 评估 SP 受体 NK-1 在肾免疫细胞上的存在。p  < 0.05) 在对照组中，肾炎反应受损。在全身施用神经激肽 1 (NK1-R) 阻滞剂后，暂时抑制 RSNA 但完全恢复。NK-1 受体主要发生在 CD11 ⁺树突细胞 (DC) 上。在肾炎中评估了 CD11c ⁺ NK1R ⁺细胞、NK-1 受体⁺巨噬细胞和 DC 的频率增加。在肾炎期间使用 NK-1R 拮抗剂阿瑞匹坦降低 CD11c ⁺ NK1R ⁺细胞、巨噬细胞浸润、趋化因子的肾脏表达和硬化标志物。因此，SP 通过削弱交感神经抑制机制促进肾脏炎症，同时，从传入神经纤维肾内释放的物质 SP 加剧了免疫过程，即通过 DC 的募集。