Kidney Week

Abstract: TH-PO0260

Parasympathetic Signaling via Renal Macrophages as a Novel Mechanism of Hypertension Pathogenesis

Session Information

• Hypertension and CVD: Mechanisms
  November 06, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

• 1601 Hypertension and CVD: Basic

Authors

• Washimine, Norito, Department of Nephrology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan

Norito Washimine, MD

• Umene, Ryusuke, Department of Nephrology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan

Ryusuke Umene, MD, PhD

• Wu, Chia-Hsien, Department of Physiology of Visceral Function and Body Fluid, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan

Chia-Hsien Wu, PhD

• Nakamura, Yasuna, Department of Physiology of Visceral Function and Body Fluid, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan

Yasuna Nakamura, MD, PhD

• Matsuo, Sayumi, Department of Nephrology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan

Sayumi Matsuo, MD

• Nishino, Tomoya, Department of Nephrology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan

Tomoya Nishino, MD, PhD

• Inoue, Tsuyoshi, Department of Physiology of Visceral Function and Body Fluid, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan

Tsuyoshi Inoue, MD, PhD

Background

Recent advances have highlighted the immune system as a critical contributor to the development of hypertension. Several studies have reported that macrophage accumulation in the cardiovascular system promotes hypertension, whereas accumulation in the skin appears to exert a buffering effect on blood pressure. These findings emphasize the need to investigate organ-specific immune responses, particularly in the kidney, which plays a crucial role in blood pressure regulation. Furthermore, the autonomic nervous system, a key regulator of blood pressure, modulates the behavior of immune cells via neurotransmitter receptors. Although we have previously reported anti-inflammatory effects mediated by neuro-immune interactions, their role in blood pressure regulation remains unclear.

Methods

We established a hypertension model in 8–10-week-old C57BL/6 male mice using angiotensin II and high salt. Immune cell accumulation in various organs was evaluated using flow cytometry. We assessed blood pressure after either pharmacological depletion of macrophages or macrophage-specific genetic knockout (KO) of autonomic nerve receptors. RNA sequencing of renal macrophages was performed in wild-type and KO mice, both before and after hypertension induction, to identify gene sets associated with blood pressure regulation. We overexpressed candidate genes in macrophages and transferred these modified macrophages into wild-type mice to examine how they affect blood pressure.

Results

Hypertensive mice showed increased macrophage accumulation in the kidney. Both pharmacological depletion of macrophages and macrophage-specific KO of parasympathetic receptor X suppressed hypertension development. RNA-seq analysis identified gene clusters that were upregulated in hypertensive mice and downregulated in receptor X-deficient macrophages. We developed a macrophage transfer model using macrophages that overexpress a candidate gene involved in blood pressure regulation.

Conclusion

These results suggest that parasympathetic signaling in macrophages may represent a novel mechanism by which the kidney contributes to hypertension.

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025s8z1629c