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Abstract: SA-PO1026

Furosemide Increases Green Fluorescent Protein-Arginine Vasopressin Expression in the Hypothalamus in Transgenic Rats

Session Information

Category: Fluid, Electrolytes, and Acid-Base

  • 702 Water/Urea/Vasopressin, Organic Solutes

Authors

  • Ueno, Hiromichi, University of Occupational & Environmental Health, Kitakyushu, fukuoka, Japan
  • Miyamoto, Tetsu, University of Occupational & Environmental Health, Kitakyushu, fukuoka, Japan
  • Bando, Kenichiro, University of Occupational and Environmental Health, Kitakyushu, Japan
  • Otsuji, Yutaka, University of Occupational and Environmental Health, Kitakyushu, Japan
  • Tamura, Masahito, University of Occupational & Environmental Health, Kitakyushu, fukuoka, Japan
  • Ueta, Yoichi, University of Occupational and Environmental Health, Kitakyushu, Japan
Background

Furosemide is an essential medication for fluid overload by inhibiting sodium reabsorption in the Henle’s loop, however, furosemide resistance is often observed in patients with kidney disease. Arginine vasopressin (AVP) is synthesized in the paraventricular nucleus (PVN) and the supraoptic nucleus (SON) of the hypothalamus, and increases water reabsorption in the collecting duct. Although previous studies have reported that furosemide activates the neurohumoral factors, AVP synthesis in the hypothalamus after peripheral administration of furosemide remains unclear.

Methods

Measurement of serum AVP levels is difficult because of its short half life (4-20 min). We therefore generated transgenic rats carrying a novel enhanced green fluorescent protein (eGFP)-AVP fusion gene. We examined AVP expression in the hypothalamus by observing fluorescence after intraperitoneal administration of furosemide in transgenic rats. We also investigated AVP gene expression using in situ hybridization histochemistry. Neuronal activity in the hypothalamus was examined by immunohistochemistry for Fos.

Results

After peripheral administration of furosemide in the transgenic rats, the fluorescence intensities in the SON and the magnocellular divisions of PVN (mPVN) were significantly increased. eGFP expressions in the SON and the mPVN were accompanied by Fos expression. Furthermore, AVP hnRNA levels in the SON and the mPVN were significantly increased after administration of furosemide.

Conclusion

We observed increased neuronal activity and AVP expression in the hypothalamus after peripheral administration of furosemide in eGFP-AVP transgenic rats. These results might account for one of the cause of furosemide resistance.