Abstract: SA-PO1101

Combination of High Fructose and High Salt Increases Renal Sodium Reabsorption and Blood Pressure That Is Dependent on Ketohexokinase

Session Information

  • Salt and Hypertension
    November 04, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Hypertension

  • 1102 Hypertension: Basic and Experimental - Renal Causes and Consequences

Authors

  • Hayasaki, Takahiro, Nagoya University Graduate School of Medicine, Nagoya-shi, Japan
  • Ishimoto, Takuji, Nagoya University Graduate School of Medicine, Nagoya-shi, Japan
  • Doke, Tomohito, Nagoya University Graduate School of Medicine, Nagoya-shi, Japan
  • Kosugi, Tomoki, Nagoya University Graduate School of Medicine, Nagoya-shi, Japan
  • Lanaspa, Miguel A., University of Colorado Denver, Aurora, Colorado, United States
  • Tsuboi, Naotake, Nagoya University Graduate School of Medicine, Nagoya-shi, Japan
  • Johnson, Richard J., University of Colorado Denver, Aurora, Colorado, United States
  • Maruyama, Shoichi, Nagoya University Graduate School of Medicine, Nagoya-shi, Japan
Background

High fructose intake has been reported to induce metabolic syndrome in laboratory animals and humans. Although it has been also reported that fructose intake enhances sodium reabsorption and causes the elevation of blood pressure (BP), its mechanism is unclear. Here, we examined whether fructose metabolism by the primary enzyme of fructose, ketohexokinase (KHK) regulates sodium reabsorption and BP by using KHK deficient mice (lacking both isoform A and C, KHK-KO).

Methods

Male, C57BL/6, wild-type mice (WT) and KHK KO were used. Study 1; WT and KHK KO were fed with control diet (CD) or 4% high salt diet (HSD), and 10% fructose water (Fr) or tap water (Wa). BP was measured every week (tail cuff), and samples were collected at 5 weeks. Pathological analysis was done, and renal and jejunal KHKs and NHE3 (sodium-hydrogen exchanger 3) expressions were assessed. Study 2; To investigate the effect of fructose intake on renal sodium reabsorption without intestinal absorption, control WT and KHK KO mice and those fed CD and Fr for 5 weeks were administered intraperitoneally with 1.5 ml of normal saline, then urine was collected 6 hours later.

Results

Study 1; KHK was colocarized immunohistochemically with NHE3 in proximal tubular cells in WT. Combination of HSD and Fr for 5 weeks induced the elevation of BP with the decrease of urinary sodium excretion and the increase of renal expression of KHK-C and NHE3 in WT, but not in KHK KO. WT fed HSD without Fr did not show the elevation of BP nevertheless of higher amount of sodium intake than WT fed HSD and Fr. Jejunal NHE3 was tend to increase in WT fed HSD and Fr than KHK KO. Study 2; Urinary sodium excretion after intraperitoneal sodium loading was reduced in WT given Fr compared with that of the control WT. In KHK KO, that reduction was not observed, and renal NHE3 expression was lower than WT.

Conclusion

These results suggest that fructose metabolism by KHK is involved in the development of salt-sensitive hypertension through increases of renal sodium reabsorption by NHE3.