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 |
Externí odkaz: |