Document Detail


Effects of ACE inhibition on proximal tubule sodium transport.
MedLine Citation:
PMID:  16263808     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Angiotensin-converting enzyme (ACE) inhibitors such as captopril, which block ANG II formation, are commonly used for treatment of hypertension. There is substantial evidence that the proximal tubule (PT) is a primary target site for captopril but the molecular mechanisms for its action in PT are not well defined. The aim of this study was to determine the physiological and molecular changes in PT provoked by acute captopril treatment in the absence of changes in blood pressure or glomerular filtration rate (GFR). Captopril (infused at 12 microg/min for 20 min) did not change blood pressure or GFR but induced an immediate (<10 min) increase in PT flow measured with a nonobstructive optical method (to 117 +/- 14% of baseline) along with a rapid diuresis from 2.1 +/- 0.6 mg/min (baseline) to 3.7 +/- 0.9 mg/min (captopril). Captopril also provoked a significant retraction of PT Na(+)/H(+) exchanger isoform 3 (NHE3), NHE regulatory factor (NHERF)-1, myosin-VI, and Na(+)-P(i) cotransporter type 2 (NaPi2), but not ACE, out of apical microvillus-enriched membranes. Proteomic analysis with MALDI-TOF MS revealed an additional eight abundant membrane-associated proteins that redistributed out of the microvillus-enriched membrane during captopril treatment: megalin, myosin II-A, clathrin, aminopeptidase N, DPPIV, ezrin, moesin, and vacuolar H(+)-ATPase subunit beta(2). In summary, captopril can rapidly depress PT reabsorption in the absence of a change in GFR or BP and provokes the redistribution of a set of transporters and transporter-associated proteins that likely participate in the decrease in PT reabsorption and may also contribute to the blood pressure-lowering effect of ACE inhibitors.
Authors:
Patrick K K Leong; Angela Devillez; Monica B Sandberg; Li E Yang; Daniel K P Yip; Jon B Klein; Alicia A McDonough
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2005-11-01
Journal Detail:
Title:  American journal of physiology. Renal physiology     Volume:  290     ISSN:  1931-857X     ISO Abbreviation:  Am. J. Physiol. Renal Physiol.     Publication Date:  2006 Apr 
Date Detail:
Created Date:  2006-03-10     Completed Date:  2006-04-13     Revised Date:  2011-04-28    
Medline Journal Info:
Nlm Unique ID:  100901990     Medline TA:  Am J Physiol Renal Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  F854-63     Citation Subset:  IM    
Affiliation:
Department of Physiology and Biophysics, University of Southern California Keck School of Medicine, Los Angeles 90089-9142, USA.
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MeSH Terms
Descriptor/Qualifier:
Angiotensin-Converting Enzyme Inhibitors / pharmacology*
Animals
Blood Pressure
Captopril / pharmacology*
Glomerular Filtration Rate
Kidney Tubules, Proximal / physiology*
Male
Mass Spectrometry
Membrane Proteins / drug effects,  physiology
Proteomics
Rats
Rats, Sprague-Dawley
Sodium / pharmacokinetics*
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Grant Support
ID/Acronym/Agency:
DK-34316/DK/NIDDK NIH HHS; DK-48522/DK/NIDDK NIH HHS; DK-60501/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 0/Membrane Proteins; 62571-86-2/Captopril; 7440-23-5/Sodium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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