HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 290/4/F854    most recent 00353.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Leong, P. K. K. Articles by McDonough, A. A. Search for Related Content PubMed PubMed Citation Articles by Leong, P. K. K. Articles by McDonough, A. A.

Effects of ACE inhibition on proximal tubule sodium transport

¹Department of Physiology and Biophysics, University of Southern California Keck School of Medicine, Los Angeles, California; ²Core Proteomics Laboratory, Kidney Disease Program, Department of Medicine, University of Louisville, Louisville, Kentucky; and ³Department of Physiology and Biophysics, University of South Florida, Tampa, Florida

Submitted 29 August 2005 ; accepted in final form 26 October 2005

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 µg/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 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.

sodium/hydrogen exchanger isoform 3; proximal tubular flow; proteomics; angiotensin II; hypertension

This article has been cited by other articles:

				A. Fekete, K. Rosta, L. Wagner, A. Prokai, P. Degrell, E. Ruzicska, E. Vegh, M. Toth, K. Ronai, K. Rusai, et al. Na+,K+-ATPase is modulated by angiotensin II in diabetic rat kidney - another reason for diabetic nephropathy? J. Physiol., November 15, 2008; 586(22): 5337 - 5348. [Abstract] [Full Text] [PDF]

				L. E. Yang, M. B. Sandberg, A. D. Can, K. Pihakaski-Maunsbach, and A. A. McDonough Effects of dietary salt on renal Na+ transporter subcellular distribution, abundance, and phosphorylation status Am J Physiol Renal Physiol, October 1, 2008; 295(4): F1003 - F1016. [Abstract] [Full Text] [PDF]

				P. L. Diaz-Sylvester, M. C. Fiori, S. M. Dieguez, A. C. Muller, M. L. Lopardo, and C. E. Amorena Effect of chronic inhibition of converting enzyme on proximal tubule acidification Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2008; 294(6): R2014 - R2020. [Abstract] [Full Text] [PDF]

				A. C. C. Girardi, L. E. Fukuda, L. V. Rossoni, G. Malnic, and N. A. Reboucas Dipeptidyl peptidase IV inhibition downregulates Na+-H+ exchanger NHE3 in rat renal proximal tubule Am J Physiol Renal Physiol, February 1, 2008; 294(2): F414 - F422. [Abstract] [Full Text] [PDF]

				K. Kotlo, S. Shukla, U. Tawar, R. A. Skidgel, and R. S. Danziger Aminopeptidase N reduces basolateral Na+-K+-ATPase in proximal tubule cells Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1047 - F1053. [Abstract] [Full Text] [PDF]

				L. E. Yang, P. K. K. Leong, and A. A. McDonough Reducing blood pressure in SHR with enalapril provokes redistribution of NHE3, NaPi2, and NCC and decreases NaPi2 and ACE abundance Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1197 - F1208. [Abstract] [Full Text] [PDF]

				X. Yang, H.-C. Huang, H. Yin, R. J. Alpern, and P. A. Preisig RhoA required for acid-induced stress fiber formation and trafficking and activation of NHE3 Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1054 - F1064. [Abstract] [Full Text] [PDF]

				M. B. Sandberg, A. D. M. Riquier, K. Pihakaski-Maunsbach, A. A. McDonough, and A. B. Maunsbach ANG II provokes acute trafficking of distal tubule Na+-Cl cotransporter to apical membrane Am J Physiol Renal Physiol, September 1, 2007; 293(3): F662 - F669. [Abstract] [Full Text] [PDF]

				M. Donowitz and X. Li Regulatory Binding Partners and Complexes of NHE3 Physiol Rev, July 1, 2007; 87(3): 825 - 872. [Abstract] [Full Text] [PDF]

				M. G. Janech, J. R. Raymond, and J. M. Arthur Proteomics in renal research Am J Physiol Renal Physiol, February 1, 2007; 292(2): F501 - F512. [Abstract] [Full Text] [PDF]