Abstract: TH-PO1029
Hydrochlorothiazide and Acute Urinary Acidification: The Voltage Hypothesis of ENaC-Dependent H+ Secretion Refuted
Session Information
- Acid Base: Basic
November 02, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Fluid, Electrolytes, and Acid-Base
- 701 Acid-Base: Basic
Authors
- Ayasse, Niklas, Aarhus University, Aarhus, Denmark
- Leipziger, Jens G., Aarhus University, Aarhus, Denmark
Background
It has been assumed that furosemide-induced urinary acidification is due to the coupling between increased electrogenic sodium transport via the epithelial sodium channel (ENaC) in the collecting duct (CD) and a subsequent increased activity of the vacuolar H+-ATPase, localized in the α-intercalated cells of the CD. However, we recently showed that urine acidification by furosemide occurs apparently independent of ENaC activity. We demonstrated that furosemide directly stimulates H+ secretion in the thick ascending limb (TAL) via the Na+/H+ exchanger NHE3. Under the assumption that urinary acidification takes place in the TAL we expect that the administration of hydrochlorothiazide (HCT) does not cause an acute change in urinary pH. We investigated the effect of HCT both under conditions of low and high ENaC expression.
Methods
Mice having been subjected to either a control diet or a low-Na+ diet were anesthetized and infused (0.5 ml/h) with a control solution. The urinary bladder was catheterized and urine pH was measured directly in the outflow of the catheter with an electrode. Mice received either HCT (30mg/kg/h) or a vehicle solution. Diuresis was simultaneously quantified. Urinary Na+ and K+ excretions were measured using flame photometry. The kidneys were harvested to quantify ENaC expression by Western Blotting.
Results
(1) Mice having been fed a low-Na+ diet showed a significant upregulation of ENaC.
(2) After the administration of HCT urine output was increased in both groups. (3) HCT caused an increase in Na+ excretion that did not reach significance. (4) K+ excretion rates increased markedly after HCT administration from 18.55±3.83 to 31.67±7.62 in the control diet group and from 22.95±3.68 to 48.71±8.36 µmol/h in the low-Na+ diet group.
(5) Importantly, no changes in urine pH were observed after the administration of HCT in both groups.
Conclusion
Despite the induction of acute kaliuresis by HCT, indicating an increased electrogenic transport of Na+ via ENaC, an acute increased H+ secretion was not observed, neither under control conditions nor under conditions of marked ENaC upregulation. Thus, this study supports our previous finding that H+ secretion by furosemide takes place in the TAL.
Funding
- Government Support - Non-U.S.