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Hydrochlorothiazide and acute urinary acidification: The “voltage hypothesis” of ENaC‐dependent H + secretion refuted
Author(s) -
Ayasse N.,
de Bruijn P. I. A.,
Berg P.,
Sørensen M. V.,
Leipziger J.
Publication year - 2018
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.13013
Subject(s) - natriuresis , epithelial sodium channel , diuresis , endocrinology , medicine , furosemide , urine , hydrochlorothiazide , excretion , chemistry , urinary system , diuretic , reabsorption , sodium , kidney , blood pressure , organic chemistry
Aim The “voltage hypothesis” of H + secretion states that urinary acidification following increased Na + delivery to the collecting duct ( CD ) is EN aC dependent leading to transepithelial voltage‐dependent increase in H + secretion. We recently showed that furosemide acidifies the urine independently of EN aC 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 EN aC expression. Methods Mice 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. EN aC 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 μmol h −1 in the control diet group and from 23.0 ± 1.3 to 48.7 ± 3.0 μmol h −1 in the low‐Na + diet group. (3) Mice fed a low‐Na + diet showed a marked upregulation of EN aC. (4) Importantly, no acute changes in urine pH were observed after the administration of HCT in either group. Conclusion Acute administration of HCT has no effect on urine pH . Similarly, substantial functional and molecular upregulation of EN aC 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.