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Author Notes:

C. A. West: Georgetown University Medical Center, Department of Medicine, 4000 Reservoir Road, NW, Washington, DC 20057, USA. caw240@georgetown.edu

Experiments were performed in the laboratories of C.B. and J.W.V. C.B., C.A.W., J.W.V. and S.M.W. were involved in the conception and design of the experiments and in drafting the article and revising it critically for important intellectual content. C.B., C.A.W. and J.W.V. were involved in the collection, analysis and interpretation of data. All authors approved the final version of this manuscript. All persons designated as authors qualify for authorship, and all those who qualify for authorship are listed.

The authors would like to thank Dr I. David Weiner for developing the software for the quantitative immunohisto-chemistry, Mr Richard Smith for his expert technical assistance and Dr Shyama Masilamani for providing the NCC antibody. We also thank Dr Sharon Matthews and Ms Tanisha Thomas in the University of Florida College of Medicine Electron Microscopy Core for preparing the tissues for immunohistochemistry.

Competing interests: None declared.

Subjects:

Research Funding:

This work was supported by the Robert and Mary Cade Professorship of Physiology and the National Institutes of Health grants T32-HL-093910, R01-HD-041571 and R01-DK-56843 to C.B. and R01-DK 46493 to S.M.W. C.A.W. was supported by NIH T32-HL-093910.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Physiology
  • EPITHELIAL SODIUM-CHANNEL
  • CORTICAL COLLECTING DUCT
  • MATERNAL PLASMA-VOLUME
  • NA-CL COTRANSPORTER
  • MOUSE KIDNEY
  • FETAL-GROWTH
  • HORMONAL CHANGES
  • ENAC PROTEIN
  • EXPRESSION
  • ALDOSTERONE

The chloride-bicarbonate exchanger pendrin is increased in the kidney of the pregnant rat

Tools:

Journal Title:

EXPERIMENTAL PHYSIOLOGY

Volume:

Volume 100, Number 10

Publisher:

, Pages 1177-1186

Type of Work:

Article | Post-print: After Peer Review

Abstract:

New Findings: What is the central question of this study? Pregnancy requires a robust plasma volume expansion driven by renal sodium retention. In the late-pregnant kidney, the aldosterone-responsive epithelial Na+ channel is increased, whereas the sodium-chloride cotransporter is decreased. Pendrin has been shown to support sodium reabsorption in the distal nephron and compensate for loss of the sodium-chloride cotransporter. We investigated the expression and abundance of pendrin in the pregnant kidney. What is the main finding and its importance? Pendrin protein, apical localization and thiazide sensitivity are increased in pregnancy. This implicates a possible role for pendrin in supporting the renal sodium chloride reabsorption and plasma volume expansion of pregnancy. Pregnancy is characterized by cumulative plasma volume expansion as a result of renal sodium retention, driven by activation of aldosterone. We previously reported that the abundance and activity of the aldosterone-responsive epithelial Na+ channel is increased, whereas the sodium-chloride cotransporter (NCC) is decreased in the kidney of the late-pregnant rat. The chloride-bicarbonate exchanger pendrin is also aldosterone responsive and has been shown to support activity of the aldosterone-responsive epithelial Na+ channel and compensate for the loss of NCC. Additionally, pendrin coupled to the sodium-dependent chloride-bicarbonate exchanger (NDCBE) mediates thiazide-sensitive sodium reabsorption in the cortical collecting duct. In this study, we investigated pendrin and NDCBE transcript expression, pendrin protein abundance, pendrin cellular localization and thiazide sensitivity in virgin, mid-pregnant and late-pregnant rats to test the hypothesis that increased pendrin activity might occur in pregnancy. By RT-PCR, NDCBE and pendrin mRNA expression was unchanged from virgins, whereas pendrin protein abundance determined by Western blotting was increased in both mid- and late-pregnant rats. The apical localization of pendrin was also increased in late-pregnant rats compared with virgins by immunohistochemistry. Pregnant rats displayed an increased natriuretic response to hydrochlorothiazide compared with virgins. Given that NCC expression is decreased in late pregnancy, an increased thiazide sensitivity may be due to inhibition of upregulated pendrin-NDCBE-coupled sodium reabsorption. Thus, increased pendrin in pregnant rats may compensate for the decreased NCC and aid in the renal sodium chloride reabsorption of pregnancy.
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