Hydrochlorothiazide and acute urinary acidification: The “voltage hypothesis” of ENaC‐dependent H<sup>+</sup> secretion refuted

Ayasse, Niklas; Bruijn, Pauline I.A. de; Berg, Peder; Sørensen, Mads Vaarby; Leipziger, Jens

doi:10.1111/apha.13013

Cited by 6 publications

(4 citation statements)

References 28 publications

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“…In control mice, with assumable low basal ENaC activity, no acute thiazide‐induced kaliuresis was detected. Interestingly, in mice kept a few days on a low Na + intake, a thiazide‐induced kaliuresis could be detected (Ayasse et al., 2017; Hunter et al., 2014). In contrast, Li et al.…”

Section: Discussionmentioning

confidence: 99%

ENaC expression correlates with the acute furosemide‐induced K⁺excretion

et al. 2021

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Section: Discussionmentioning

confidence: 99%

ENaC expression correlates with the acute furosemide‐induced K⁺excretion

et al. 2021

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“…The experimental setup was as previously described. 4,26 In brief, mice were anesthetized with a ketamine-xylazine mix, and a tail-vein catheter and bladder catheter were placed. Anesthesia was maintained by continuous intravenous infusion using a syringe pump (Model 33 Twin Syringe Pump, Harvard Apparatus).…”

Section: Methodsmentioning

confidence: 99%

Loss of the Secretin Receptor Impairs Renal Bicarbonate Excretion and Aggravates Metabolic Alkalosis in Mice during Acute Base-Loading

Berg

Jensen

Andersen

et al. 2023

JASN

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Background The secretin receptor (SCTR) is functionally expressed in the basolateral membrane of the β-intercalated cells of the kidney cortical collecting duct and stimulates urine alkalization by activating the β-intercalated cells. Interestingly, the plasma secretin level increases during acute metabolic alkalosis, but its role in systemic acid–base homeostasis was unclear. We hypothesized that the SCTR system is essential for renal base excretion during acute metabolic alkalosis. Methods We conducted bladder catheterization experiments, metabolic cage studies, blood gas analysis, barometric respirometry, perfusion of isolated cortical collecting ducts, immunoblotting, and immunohistochemistry in SCTR wild-type and knockout (KO) mice. We also perfused isolated rat small intestines to study secretin release. Results In wild-type mice, secretin acutely increased urine pH and pendrin function in isolated perfused cortical collecting ducts. These effects were absent in KO mice, which also did not sufficiently increase renal base excretion during acute base loading. In line with these findings, KO mice developed prolonged metabolic alkalosis when exposed to acute oral or intraperitoneal base loading. Furthermore, KO mice exhibited transient but marked hypoventilation after acute base loading. In rats, increased blood alkalinity of the perfused upper small intestine increased venous secretin release. Conclusions Our results suggest that loss of SCTR impairs the appropriate increase of renal base excretion during acute base loading and that SCTR is necessary for acute correction of metabolic alkalosis. In addition, our findings suggest that blood alkalinity increases secretin release from the small intestine and that secretin action is critical for bicarbonate homeostasis.

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“…ENaC activity contributes to a lumen-negative transepithelial voltage, thereby promoting proton secretion in the CD, although this theory has been recently challenged. 20…”

Section: Mechanistic Insights Into Intercalated Cells and Their Role ...mentioning

confidence: 99%

“…ENaC activity contributes to a lumen-negative transepithelial voltage, thereby promoting proton secretion in the CD, although this theory has been recently challenged. 20 In B-ICs, the apical pendrin and the Na 1 -driven chloride/bicarbonate exchanger mediate thiazide-sensitive electroneutral NaCl reabsorption. 21 Two cycles of pendrin exchange and one cycle of Na 1 -driven chloride/bicarbonate exchanger coordinated with basolateral AE4 result in the net uptake of one sodium and one chloride ion and secretion of two bicarbonate ions.…”

Section: Salt Homeostasismentioning

confidence: 99%

Urinary Tract Infections: Renal Intercalated Cells Protect against Pathogens

Chelangarimiyandoab,

Mungara,

Batta

et al. 2023

JASN

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Urinary tract infections (UTIs) affect more than 1 in 2 women during their lifetime. Among these, more than 10 % of patients carry antibiotic-resistant bacterial strains, highlighting the urgent need to identify alternative treatments. While innate defence mechanisms are well characterized in the lower urinary tract, it is becoming evident that the collecting duct, the first renal segment encountered by invading uropathogenic bacteria, also contributes to bacterial clearance. However, the role of this segment is beginning to be understood. This review summarizes the current knowledge on collecting duct intercalated cells in urinary tract bacterial clearance. Understanding the innate protective role of the uroepithelium and of the collecting duct offers new opportunities for alternative therapeutic strategies.

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Hydrochlorothiazide and acute urinary acidification: The “voltage hypothesis” of ENaC‐dependent H⁺ secretion refuted

Cited by 6 publications

References 28 publications

ENaC expression correlates with the acute furosemide‐induced K⁺excretion

ENaC expression correlates with the acute furosemide‐induced K⁺excretion

Loss of the Secretin Receptor Impairs Renal Bicarbonate Excretion and Aggravates Metabolic Alkalosis in Mice during Acute Base-Loading

Urinary Tract Infections: Renal Intercalated Cells Protect against Pathogens

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Hydrochlorothiazide and acute urinary acidification: The “voltage hypothesis” of ENaC‐dependent H+ secretion refuted

Cited by 6 publications

References 28 publications

ENaC expression correlates with the acute furosemide‐induced K+excretion

ENaC expression correlates with the acute furosemide‐induced K+excretion

Loss of the Secretin Receptor Impairs Renal Bicarbonate Excretion and Aggravates Metabolic Alkalosis in Mice during Acute Base-Loading

Urinary Tract Infections: Renal Intercalated Cells Protect against Pathogens

Contact Info

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Hydrochlorothiazide and acute urinary acidification: The “voltage hypothesis” of ENaC‐dependent H⁺ secretion refuted

ENaC expression correlates with the acute furosemide‐induced K⁺excretion

ENaC expression correlates with the acute furosemide‐induced K⁺excretion