Kidney Week

Abstract: FR-PO340

Fabry Disease Mouse Is Resistant to High-Salt Diet-Induced Hypertension Probably via Dysfunctional Sodium Transporters and Aquaporin 2

Session Information

• Genetic Diseases: Models, Mechanisms, Treatments
  November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1102 Genetic Diseases of the Kidneys: Non-Cystic

Authors

• Park, Junkyu, The Catholic University of Korea, Seoul, Korea (the Republic of)

Junkyu Park,

• Jo, Wonji, The Catholic University of Korea, Seoul, Korea (the Republic of)

Wonji Jo,

• Chung, Sungjin, The Catholic University of Korea, Seoul, Korea (the Republic of)

Sungjin Chung,

• Koh, Eun Sil, The Catholic University of Korea, Seoul, Korea (the Republic of)

Eun Sil Koh,

Background

Fabry disease is a rare X-linked lysosomal storage disorder resulting from an error in glycosphingolipid metabolism caused by the GLA gene mutation. Patients with Fabry disease often have near normal or even low systemic blood pressure although the mechanism underlying such observed finding remains unexplained. This study examined whether a high salt intake could affect transport of sodium and water and induce hypertension in mice with Fabry disease.

Methods

Fabry disease model mice (B6;129-Gla^tm1Kul/J) and wild-type (WT) mice received 8% or normal NaCl salt diet for 2 weeks.

Results

A high-salt diet for 2 weeks generated higher blood pressure in WT mice but not in Fabry disease mice. Free water clearance (FWC) and electrolyte free water clearance (EFWC) in groups fed with a high salt diet were lower than those in groups fed with a normal salt diet. Both high salt-fed WT and Fabry disease mice had decreased γ-subunit of epithelial Na channel (ENaC) compared with normal salt-fed groups. In Fabry disease mice fed a high-salt diet, there was an decrease in renal expressions of Na⁺/H⁺ exchanger isoform 3 (NHE3) and Na⁺-Cl^- cotransporter (NCC) compared with WT mice fed a high-salt diet. Although renal expression of vasopressin V2 receptor (V2R) was upregulated in Fabry mice fed with a high salt diet, renal aquaporin 2 (AQP2) level failed to increase up to the level in WT mice fed with a high salt diet.

Conclusion

These findings suggest that the decreased expression of NHE3 and NCC and impaired response of AQP2 in kidneys of Fabry disease to a salt load could be one of mechanisms by which Fabry disease could have resistance to the development of hypertension.