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Abstract: PO2135

Neurogenic Tachykinin Mechanisms in Experimental Nephritis of Rats

Session Information

Category: Hypertension and CVD

  • 1403 Hypertension and CVD: Mechanisms

Authors

  • Rodionova, Kristina, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Nuremberg, Bavaria, Germany
  • Ditting, Tilmann, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Nuremberg, Bavaria, Germany
  • Tiegs, Gisa, Universitatsklinikum Hamburg Eppendorf Zentrum fur Experimentelle Medizin, Hamburg, Hamburg, Germany
  • Hilgers, Karl F., Friedrich-Alexander-Universitat Erlangen-Nurnberg, Nuremberg, Bavaria, Germany
  • Schiffer, Mario, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Nuremberg, Bavaria, Germany
  • Ott, Christian, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Nuremberg, Bavaria, Germany
  • Schmieder, Roland E., Friedrich-Alexander-Universitat Erlangen-Nurnberg, Nuremberg, Bavaria, Germany
  • Amann, Kerstin U., Friedrich-Alexander-Universitat Erlangen-Nurnberg, Nuremberg, Bavaria, Germany
  • Veelken, Roland, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Nuremberg, Bavaria, Germany
Background

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.

Methods

Nephritis was induced by OX-7 antibodies in rats, six days later instrumented for recording of blood pressure (BP), heart rate (HR), drug administration; intrarenal administration (IRA) of the TRPV1 agonist capsaicin to stimulate afferent renal nerve pathways containing SP and implantation of electrodes for renal sympathetic nerve recordings (RSNA). The presence of the SP receptor NK-1 on renal immune cells was assessed by FACS.

Results

IRA capsaicin decreased RSNA from 62.4±5.1 mV*sec to 21.6±1.5 mV*sec (*p<0.05) in controls, a response impaired in nephritis. Suppressed RSNA in nephritic rats and controls transiently but completely recovered after systemic administration of a neurokin 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 were 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.

Conclusion

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.

Funding

  • Government Support - Non-U.S.