Abstract: SA-PO1051

Furosemide Is a Potassium-Sparing Diuretic in Mice on a Low Sodium High Potassium Diet

Session Information

  • Na+, K+, Cl-
    November 04, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Fluid, Electrolytes, and Acid-Base

  • 703 Na+, K+, Cl- Basic

Authors

  • Wang, Bangchen, University of Nebraska Medical Center, Omaha, Nebraska, United States
  • Wen, Donghai, University of Nebraska Medical Center, Omaha, Nebraska, United States
  • Wang-France, Jun, University of Nebraska Medical Center, Omaha, Nebraska, United States
  • Sansom, Steven C., University of Nebraska Medical Center, Omaha, Nebraska, United States
Background

Because of its cardio-protective benefits, a low Na, high K diet (LNaHK) is often warranted in conjunction with diuretics for hypertensive patients. However, it is necessary to understand the renal handling of such diets in order to choose the best diuretic. As previously shown by our lab, furosemide, a K-wasting diuretic, decreased renal K clearance (CLK) in mice on LNaHK by inhibiting the net K+ secretion in the thick ascending limb (TAL). Given that furosemide acidifies the urine by increasing acid secretion from TAL and that distal K+ secretion is affected by urine pH, we hypothesized that furosemide reduces distal K+ secretion via the large conductance, Ca-activated K channel (BK).

Methods

Wild-type (WT) and BK-β4 knockout mice (KO) were kept on LNaHK (0.01% Na, 5% K) for 7 days. After intraperitoneal injections of vehicle, furosemide (furo; 15 mg/kg), amiloride (amil; 5 mg/kg), or amil + furo, mice were placed into metabolic cages to collect urine for 12 hours. Another group of WT were kept on LNaHK for 7 days and placed into metabolic cages to collect urine for 24 hours with access to either regular water or alkaline furosemide water (0.1 mg/mL, pH 8.8). The mice were then sacrificed and the [K+] and pH were measured from blood and urine samples. Fluorescence immunohistochemistry (FIHC) was performed on paraffin-embedded kidney sections stained for BK-α.

Results

In WT, the furo group exhibited lower urine pH and lower CLK than vehicle. In KO, the furo group exhibited a lower urine pH but a similar CLK compared to vehicle. The amil + furo group had a lower CLK than the amil group of both WT and KO. There is a positive linear association between CLK and urine pH in WT but not BK-β4 KO on LNaHK. FIHC showed that BK-α was localized in the apical membrane of connecting tubule cells (CNT) in WT vehicle group. However, BK-α was localized in the cytoplasm of CNT in the WT furo group and both groups of KO. Urine pH and CLK were not different between WT on LNaHK with regular water and alkaline furosemide water.

Conclusion

These results suggest that in mice on LNaHK, in addition to suppressing net K+ secretion in TAL, furosemide inhibits BK-αβ4-mediated K+ secretion in the distal nephron by acidifying the urine. These actions together make furosemide a K-sparing diuretic in the setting of LNaHK.

Funding

  • NIDDK Support