Journal
ACTA PHYSIOLOGICA
Volume 223, Issue 1, Pages -Publisher
WILEY
DOI: 10.1111/apha.13013
Keywords
acid excretion; distal convoluted tubule; epithelial Na+ channel; Na+; Cl- cotransporter
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Funding
- Danish Medical Research Council [FSS 6110-00131B]
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AimThe voltage hypothesis of H+ secretion states that urinary acidification following increased Na+ delivery to the collecting duct (CD) is ENaC dependent leading to transepithelial voltage-dependent increase in H+ secretion. We recently showed that furosemide acidifies the urine independently of ENaC activity. If the voltage hypothesis holds, hydrochlorothiazide (HCT) must acidify the urine. We here tested the acute effect of HCT on urine pH under normal and high ENaC expression. MethodsMice subjected to a control or a low-Na+ diet were anesthetized and infused (0.5 mL h(-1)) with saline. Catheterization of the urinary bladder allowed real-time measurement of diuresis and urine pH. Mice received either HCT (1 mg mL(-1)) or vehicle. Urinary Na+ and K+ excretions were determined by flame photometry. ENaC expression levels were measured by semi-quantitative Western blotting. Results(1) HCT increased diuresis and natriuresis in both diet groups. (2) K+ excretion rates increased after HCT administration from 18.6 1.3 to 31.7 +/- 2.5 mol h(-1) in the control diet group and from 23.0 +/- 1.3 to 48.7 +/- 3.0 mol h(-1) in the low-Na+ diet group. (3) Mice fed a low-Na+ diet showed a marked upregulation of ENaC. (4) Importantly, no acute changes in urine pH were observed after the administration of HCT in either group. ConclusionAcute administration of HCT has no effect on urine pH. Similarly, substantial functional and molecular upregulation of ENaC did not cause HCT to acutely change urine pH. Thus, an increased Na+ load to the CD does not alter urine pH. This supports our previous finding and likely falsifies the voltage hypothesis of H+ secretion.
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