Neurogenic tachykinin mechanisms in experimental nephritis of rats
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INTEGRATIVE PHYSIOLOGY
Neurogenic tachykinin mechanisms in experimental nephritis of rats Kristina Rodionova 1 & Karl F. Hilgers 1 & Eva-Maria Paulus 1 & Gisa Tiegs 2 & Christian Ott 1,3 & Roland Schmieder 1 & Mario Schiffer 1 & Kerstin Amann 4 & Roland Veelken 1,3 & Tilmann Ditting 1,3 Received: 6 May 2020 / Revised: 7 August 2020 / Accepted: 30 September 2020 # The Author(s) 2020
Abstract 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. Keywords Renal innervation . Nephritis . Tachykinins . Dendritic cells . Sympathetic nerve activity
Introduction Tilmann Ditting & Roland Veelken contributed equally to this publication Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00424-020-02469-z) contains supplementary material, which is available to authorized users. * Roland Veelken [email protected] 1
Department of Internal Medicine 4 (Nephrology und Hypertension), Friedrich-Alexander University Erlangen, Loschgestraße 8, 91054 Erlangen, Germany
2
Center of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
3
Department of Internal Medicine 4 (Nephrology und Hypertension), Paracelsus Private Medical School, Klinikum Nuremberg, Nuremberg, Germany
4
Department of Nephropathology, University of Erlangen, Erlangen, Germany
Effects of renal sympathetic nerve fibers on renal excretory function are very well documented [4, 11], bu
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