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Kidney Week

Abstract: FR-PO187

Anti-Inflammatory and Renal Protective Mechanisms by Controlling Parasympathetic and Sympathetic Balance

Session Information

  • AKI: Mechanisms - II
    November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Umene, Ryusuke, Department of Nephrology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Nagasaki, Japan
  • Wu, Chia-Hsien, Department of Physiology of Visceral Function and Body Fluid, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Nagasaki, Japan
  • Torigoe, Kenta, Department of Nephrology, Nagasaki University Hospital, Nagasaki, Nagasaki, Japan
  • Muta, Kumiko, Department of Nephrology, Nagasaki University Hospital, Nagasaki, Nagasaki, Japan
  • Nishino, Tomoya, Department of Nephrology, Nagasaki University Hospital, Nagasaki, Nagasaki, Japan
  • Inoue, Tsuyoshi, Department of Physiology of Visceral Function and Body Fluid, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Nagasaki, Japan
Background

Acute kidney injury (AKI) lacks effective treatment. To understand renal homeostasis and develop therapeutic strategies, we investigate renal protection and anti-inflammatory effects mediated by the autonomic nervous and immune systems. Vagus and sympathetic nerve activation provide kidney protection, and stimulating both nerves yields synergistic anti-inflammatory effects in macrophages. However, achieving this synergy through autonomic nerve stimulation in vivo remains uncertain. This study aims to determine the optimal autonomic balance for kidney protection and explore in vivo autonomic nerve stimulation as a novel renal disease treatment.

Methods

In vitro experiments treated RAW 264 cells and HK-2 cells with autonomic nerve stimulants, assessing changes in renal injury markers, cytokines, and cellular properties. GTS-21 (α7nicotinic acetylcholine receptor: α7nAChR agonist) and salbutamol (β2 adrenergic receptor: β2AR agonist) were used. In vivo experiments used LPS-induced septic mice or renal ischemia-reperfusion injury as AKI models. Macrophage-specific α7nAChR and/or β2AR knockout mice were used to examine parasympathetic and sympathetic nerve stimulation effects on the kidney.

Results

In vitro, combining GTS-21 and salbutamol with LPS showed concentration-dependent, synergistic anti-inflammatory effects in RAW 264 cells. LPS and salbutamol treatment of HK-2 cells resulted in a concentration-dependent decrease in NGAL. Simultaneous administration of both agonists tended to further decrease NGAL expression. However, in vivo experiments with septic mice did not demonstrate synergistic anti-inflammatory effects when GTS-21 and salbutamol were administered together. Additionally, LysM-Cre: α7nAChR/β2AR flox mice showed attenuated renal injury compared to controls in bilateral ischemia-reperfusion injury.

Conclusion

Simultaneous parasympathetic and sympathetic stimulation synergistically reduced inflammation in macrophages and tubular cell damages. However, in vivo experiments did not support this synergistic effect. Autonomic nerve stimulation appears to have indirect anti-inflammatory and renal protective effects mediated by the immune system, as well as direct protective effects on the kidney. Maintaining a precise balance of these effects is crucial for biological homeostasis.