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Renal NCC is unchanged in the midpregnant rat and decreased in the late pregnant rat despite avid renal Na+ retention
- Source :
- American Journal of Physiology-Renal Physiology. 309:F63-F70
- Publication Year :
- 2015
- Publisher :
- American Physiological Society, 2015.
-
Abstract
- Pregnancy is characterized by plasma volume expansion due to Na+ retention, driven by aldosterone. The aldosterone-responsive epithelial Na+ channel is activated in the kidney in pregnancy. In the present study, we investigated the aldosterone-responsive Na+-Cl− cotransporter (NCC) in mid- and late pregnant rats compared with virgin rats. We determined the abundance of total NCC, phosphorylated NCC (pNCC; pT53, pS71 and pS89), phosphorylated STE20/SPS-1-related proline-alanine-rich protein kinase (pSPAK; pS373), and phosphorylated oxidative stress-related kinase (pOSR1; pS325) in the kidney cortex. We also measured mRNA expression of NCC and members of the SPAK/NCC regulatory kinase network, serum and glucocorticoid-regulated kinase (SGK)1, total with no lysine kinase (WNK)1, WNK3, and WNK4. Additionally, we performed immunohistochemistry for NCC kidneys from virgin and pregnant rats. Total NCC, pNCC, and pSPAK/OSR1 abundance were unchanged in midpregnant versus virgin rats. In late pregnant versus virgin rats, total NCC and pNCC were decreased; however, pSPAK/OSR1 was unchanged. We detected no differences in mRNA expression of NCC, SGK1, total WNK1, WNK3, and WNK4. By immunohistochemistry, NCC was mainly localized to the apical region in virgin rats, and density in the apical region was reduced in late pregnancy. Therefore, despite high circulating aldosterone levels in pregnancy, the aldosterone-responsive transporter NCC is not increased in total or activated (phosphorylated) abundance or in apical localization in midpregnant rats, and all are reduced in late pregnancy. This contrasts to the mineralocorticoid-mediated activation of the epithelial Na+ channel, which we have previously reported. Why and how NCC escapes aldosterone activation in pregnancy is not clear but may relate to regional differences in aldosterone sensitivity the increased K+ intake or other undefined mechanisms.
- Subjects :
- medicine.medical_specialty
Physiology
Protein Serine-Threonine Kinases
Kidney
Rats, Sprague-Dawley
chemistry.chemical_compound
Pregnancy
Internal medicine
parasitic diseases
medicine
Animals
Solute Carrier Family 12, Member 3
Phosphorylation
Protein kinase A
Aldosterone
urogenital system
Chemistry
Kinase
Sodium
Articles
WNK1
WNK4
Endocrinology
medicine.anatomical_structure
embryonic structures
SGK1
Pregnancy, Animal
Female
Cotransporter
Protein Kinases
Subjects
Details
- ISSN :
- 15221466 and 1931857X
- Volume :
- 309
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Renal Physiology
- Accession number :
- edsair.doi.dedup.....15269d5a04bb233889e91e3992769140
- Full Text :
- https://doi.org/10.1152/ajprenal.00147.2015