Kidney Week

Abstract: FR-PO093

Upregulation of Hypothalamic Arginine Vasopressin by Bilateral Nephrectomy in Transgenic Rats Expressing Arginine Vasopressin-Enhanced Green Fluorescent Protein

Session Information

• AKI: Tubules, Metabolism, New Models
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Sanada, Kenya, University of Occupational and Environmental Health, Japan, Kitakyushu-shi, Japan

Kenya Sanada,

• Ueno, Hiromichi, University of Occupational and Environmental Health, Japan, Kitakyushu-shi, Japan

Hiromichi Ueno,

• Miyamoto, Tetsu, University of Occupational and Environmental Health, Japan, Kitakyushu-shi, Japan

Tetsu Miyamoto,

• Bando, Kenichiro, University of Occupational and Environmental Health, Japan, Kitakyushu-shi, Japan

Kenichiro Bando,

• Fujimoto, Yoko, University of Occupational and Environmental Health, Japan, Kitakyushu-shi, Japan

Yoko Fujimoto,

• Ueta, Yoichi, University of Occupational and Environmental Health, Japan, Kitakyushu-shi, Japan

Yoichi Ueta,

• Otsuji, Yutaka, University of Occupational and Environmental Health, Japan, Kitakyushu-shi, Japan

Yutaka Otsuji,

• Tamura, Masahito, University of Occupational and Environmental Health, Japan, Kitakyushu-shi, Japan

Masahito Tamura,

Background

Acute loss of kidney function is a critical internal stressor. The paraventricular nucleus (PVN) of the hypothalamus is an integrative site of the neuroendocrine and autonomic nervous systems that deals with a variety of aversive stressors. Hypothalamic arginine vasopressin (AVP) and corticotropin-releasing hormone (CRH) in the parvocellular division of the paraventricular nucleus (pPVN) play important roles in the regulation of stress responses. However, hypothalamic AVP dynamics after acute kidney injury remain unclear.

Methods

We generated transgenic rats that express the AVP-enhanced green fluorescent protein (eGFP) fusion gene. Since eGFP fluorescent intensity is a quantitative indicator of AVP synthesis in the transgenic rats, we evaluated AVP-eGFP fluorescence in the hypothalamus after the rats had undergone bilateral nephrectomy. We then examined AVP gene expression by in situ hybridization histochemistry. Finally, we quantified Fos-Like immunoreactivity (IR) cells, which are used as a marker of neural activity, in several brain regions which modulate biological responses to severe stressors by controlling AVP synthesis.

Results

After bilateral nephrectomy, eGFP fluorescent intensities were significantly increased in the pPVN, but not in the magnocellular PVN. The mRNA levels of eGFP, AVP, and CRH in the pPVN were significantly increased after bilateral nephrectomy. Bilateral nephrectomy also caused a marked increase in Fos-IR in the locus coeruleus, nucleus of the solitary tract, area postrema, and rostral ventrolateral medulla, which are responsible for modulating sympathetic nervous system activity.

Conclusion

Bilateral nephrectomy caused upregulation of AVP synthesis and neuronal activity. Further studies are needed to identify the neural and/or humoral factors that activate the central AVP system after bilateral nephrectomy.