Long-Term Regulation of ENaC Expression in Kidney by Angiotensin II

Autor: Randall K. Packer, Shana Ageloff, Mark A. Knepper, Heddwen L. Brooks, S. Turban, Robert A. Fenton, Shyama Masilamani, Jakob Nielsen, Kathleen Beutler
Rok vydání: 2003
Předmět:
Male
Epithelial sodium channel
Angiotensin receptor
Time Factors
Bicarbonates/blood
Sodium Chloride Symporter Inhibitors
Sodium Channels/genetics
Gene Expression Regulation/drug effects
Tetrazoles
RNA
Messenger/drug effects

Kidney/drug effects
Spironolactone
Kidney
Spironolactone/pharmacology
Sodium Channels
Rats
Sprague-Dawley

Mineralocorticoid Receptor Antagonists/pharmacology
Diuretics
Kidney Tubules
Distal

Infusion Pumps
Mineralocorticoid Receptor Antagonists
Kidney Medulla/drug effects
Kidney Medulla
Benzimidazoles/pharmacology
Angiotensin Receptor Antagonists
Symporters
Chemistry
Angiotensin II
Sodium Chloride Symporter Inhibitors/pharmacology
Sodium Chloride Symporters
medicine.drug
medicine.medical_specialty
Kidney Cortex
medicine.drug_class
Injections
Subcutaneous

Immunoblotting
Benzothiadiazines
Internal medicine
Sodium Chloride
Dietary/administration & dosage

Internal Medicine
medicine
Animals
Kidney Tubules
Distal/drug effects

RNA
Messenger

Sodium Chloride
Dietary

Epithelial Sodium Channels
Angiotensin II receptor type 1
Quaternary Ammonium Compounds/urine
Biphenyl Compounds
Symporters/metabolism
Kidney metabolism
Tetrazoles/pharmacology
Rats
Potassium/urine
Quaternary Ammonium Compounds
Bicarbonates
Protein Subunits
Candesartan
Endocrinology
Gene Expression Regulation
Mineralocorticoid
Potassium
Angiotensin II/pharmacology
Protein Subunits/genetics
Benzimidazoles
Kidney Cortex/drug effects
Zdroj: Beutler, K T, Masilamani, S, Turban, S, Nielsen, J, Brooks, H L, Ageloff, S, Fenton, R A, Packer, R K & Knepper, M A 2003, ' Long-term regulation of ENaC expression in kidney by angiotensin II ', Hypertension, vol. 41, no. 5, pp. 1143-50 . https://doi.org/10.1161/01.HYP.0000066129.12106.E2
ISSN: 1524-4563
0194-911X
DOI: 10.1161/01.hyp.0000066129.12106.e2
Popis: We carried out semiquantitative immunoblotting of kidney to identify apical sodium transporter proteins whose abundances are regulated by angiotensin II. In NaCl-restricted rats (0.5 mEq Na/200 g BW/d), the type 1 angiotensin II receptor (AT 1 receptor) antagonist, candesartan, (1 mg/kg of body weight per day SC for 2 days) markedly decreased the abundance of the α subunit of the epithelial sodium channel (ENaC). This subunit has been shown to be rate-limiting for assembly of mature ENaC complexes. In addition, systemic infusion of angiotensin II increased αENaC protein abundance in rat kidney cortex. The decrease in αENaC protein abundance in response to AT 1 receptor blockade was associated with a fall in αENaC mRNA abundance (real-time RT-PCR), consistent with transcriptionally mediated regulation. The effect of AT 1 receptor blockade on αENaC expression was not blocked by spironolactone, suggesting a direct role of the AT 1 receptor in regulation of αENaC gene expression. Candesartan administration was also found to increase the abundances of the β and γ subunits. The increase in β and γENaC protein abundance was not associated with a significant increase in the renal abundances of the corresponding mRNAs, suggesting a posttranscriptional mechanism. Immunocytochemistry confirmed the increase in β and γENaC protein abundance and demonstrated candesartan-induced ENaC internalization in collecting duct cells. The results support the view that the angiotensin II receptor regulates ENaC abundance, consistent with a role for angiotensin II in regulation of collecting duct function.
Databáze: OpenAIRE