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Ablation of the Cl-/HCO3- Exchanger Pendrin Enhances Hydrochlorothiazide-Induced Diuresis.


ABSTRACT:

Background/aims

The Cl-/HCO3- exchanger pendrin and the thiazide-sensitive Na-Cl cotransporter NCC are expressed in the kidney distal nephron and mediate salt absorption. We hypothesized that deletion of pendrin leaves NCC as the major salt absorbing transporter in the distal nephron and therefore enhances salt excretion by hydrochlorothiazide (HCTZ).

Methods

Metabolic cage studies were performed in wild type, pendrin KO and NCC KO mice at baseline and following HCTZ treatment. In parallel studies, systemic blood pressure was measured in mice treated with HCTZ with the tail cuff method.

Results

Urine output, salt excretion and water intake were comparable in all groups under baseline condition. Urine output and water intake increased significantly only in pendrin KO mice in response to HCTZ, but not in WT or NCC KO mice. Sodium and chloride excretion increased in HCTZ-treated pendrin KO mice, but they remained unchanged in WT or NCC KO mice. Pendrin KO mice treated with HCTZ developed volume depletion, as determined by increased expression of renin mRNA and protein. The expression of ENaC and pendrin increased in HCTZ-treated WT mice. HCTZ treatment did not significantly modify blood pressure in any of the experimental group.

Conclusion

The ablation of the Cl-/HCO3- exchanger Pendrin enhances the magnitude of salt wasting by HCTZ.

SUBMITTER: Alshahrani S 

PROVIDER: S-EPMC10947751 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Ablation of the Cl-/HCO3- Exchanger Pendrin Enhances Hydrochlorothiazide-Induced Diuresis.

Alshahrani Saeed S   Soleimani Manoocher M  

Kidney & blood pressure research 20170727 3


<h4>Background/aims</h4>The Cl-/HCO3- exchanger pendrin and the thiazide-sensitive Na-Cl cotransporter NCC are expressed in the kidney distal nephron and mediate salt absorption. We hypothesized that deletion of pendrin leaves NCC as the major salt absorbing transporter in the distal nephron and therefore enhances salt excretion by hydrochlorothiazide (HCTZ).<h4>Methods</h4>Metabolic cage studies were performed in wild type, pendrin KO and NCC KO mice at baseline and following HCTZ treatment. In  ...[more]

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