|
|
||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Internal Medicine, Seoul National University, Clinical Research Institute of Seoul National University Hospital, 2 Department of Internal Medicine, Eulji Medical College, 5 Department of Internal Medicine, Hallym University Hangang Sacred Heart Hospital, Seoul, 110-744; 3 Department of Internal Medicine, Chungbuk National University, Cheongju 361-711, South Korea; 4 and Laboratory of Kidney and Electrolyte Metabolism, National Institutes of Health, Bethesda, Maryland 20892
Furosemide
and hydrochlorothiazide (HCTZ) exert their diuretic actions by binding
to apical Na+ transporters, viz., the
Na+-K+-2Cl
cotransporter in
the thick ascending limb and the Na+-Cl
cotransporter in the distal convoluted tubule, respectively. We carried
out semiquantitative immunoblotting and immunohistochemistry of rat
kidneys to investigate whether chronic administration of furosemide or
HCTZ is associated with compensatory changes in the abundance of
Na+ transporters downstream from the primary site of
action. Osmotic minipumps were implanted into Sprague-Dawley rats to
deliver furosemide (12 mg/day) or HCTZ (3.75 mg/day) for 7 days. To
prevent volume depletion, all animals were offered tap water and a
solution containing 0.8% NaCl and 0.1% KCl as drinking fluid. The
diuretic/natriuretic response was quantified in response to both agents
by using quantitative urine collections. Semiquantitative
immunoblotting revealed that the abundances of thick ascending limb
Na+-K+-2Cl
cotransporter and all
three subunits of the epithelial Na+ channel (ENaC) were
increased by furosemide infusion. HCTZ infusion increased the
abundances of thiazide-sensitive Na+-Cl
cotransporter and
-ENaC in the cortex and
- and
-ENaC in the outer medulla. Consistent with these results,
-ENaC
immunohistochemistry showed a remarkable increase in immunoreactivity
in the principal cells of collecting ducts with either diuretic
treatment. These increases in the abundance of Na+
transporters in response to chronic diuretic treatment may account for
the generation of diuretic tolerance associated with long-term diuretic use.
collecting duct; epithelial sodium channel; distal convoluted tubule; thiazide-sensitive sodium-chloride cotransporter
This article has been cited by other articles:
![]() |
F. Luo, Y. Wang, X. Wang, K. Sun, X. Zhou, and R. Hui A Functional Variant of NEDD4L Is Associated With Hypertension, Antihypertensive Response, and Orthostatic Hypotension Hypertension, October 1, 2009; 54(4): 796 - 801. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. A. Wagner, D. Loffing-Cueni, Q. Yan, N. Schulz, P. Fakitsas, M. Carrel, T. Wang, F. Verrey, J. P. Geibel, G. Giebisch, et al. Mouse model of type II Bartter's syndrome. II. Altered expression of renal sodium- and water-transporting proteins Am J Physiol Renal Physiol, June 1, 2008; 294(6): F1373 - F1380. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. Pech, W. Zheng, T. D. Pham, J. W. Verlander, and S. M. Wall Angiotensin II Activates H+-ATPase in Type A Intercalated Cells J. Am. Soc. Nephrol., January 1, 2008; 19(1): 84 - 91. [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] |
||||
![]() |
Y. H. Kim, V. Pech, K. B. Spencer, W. H. Beierwaltes, L. A. Everett, E. D. Green, W. Shin, J. W. Verlander, R. L. Sutliff, and S. M. Wall Reduced ENaC protein abundance contributes to the lower blood pressure observed in pendrin-null mice Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1314 - F1324. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Andrade, A. C. Rodrigues Jr., T. R. C. Sanches, R. B. Souza, and A. C. Seguro Leptospirosis leads to dysregulation of sodium transporters in the kidney and lung Am J Physiol Renal Physiol, February 1, 2007; 292(2): F586 - F592. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Song, X. Hu, S. Riazi, S. Tiwari, J. B. Wade, and C. A. Ecelbarger Regulation of blood pressure, the epithelial sodium channel (ENaC), and other key renal sodium transporters by chronic insulin infusion in rats Am J Physiol Renal Physiol, May 1, 2006; 290(5): F1055 - F1064. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Gamba Molecular Physiology and Pathophysiology of Electroneutral Cation-Chloride Cotransporters Physiol Rev, April 1, 2005; 85(2): 423 - 493. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Jeck, K. P. Schlingmann, S. C. Reinalter, M. Komhoff, M. Peters, S. Waldegger, and H. W. Seyberth Salt handling in the distal nephron: lessons learned from inherited human disorders Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2005; 288(4): R782 - R795. [Abstract] [Full Text] [PDF] |
||||
![]() |
Z. Zhu, S. Zhu, D. Liu, T. Cao, L. Wang, and M. Tepel Thiazide-Like Diuretics Attenuate Agonist-Induced Vasoconstriction by Calcium Desensitization Linked to Rho Kinase Hypertension, February 1, 2005; 45(2): 233 - 239. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. A. Sonalker, S. P. Tofovic, and E. K. Jackson Increased Expression of the Sodium Transporter BSC-1 in Spontaneously Hypertensive Rats J. Pharmacol. Exp. Ther., December 1, 2004; 311(3): 1052 - 1061. [Abstract] [Full Text] [PDF] |
||||
![]() |
C.-T. Lee, S. Shang, L.-W. Lai, K.-C. Yong, and Y.-H. H. Lien Effect of thiazide on renal gene expression of apical calcium channels and calbindins Am J Physiol Renal Physiol, December 1, 2004; 287(6): F1164 - F1170. [Abstract] [Full Text] [PDF] |
||||
![]() |
G.-H. Kim, J. W. Lee, Y. K. Oh, H. R. Chang, K. W. Joo, K. Y. Na, J.-H. Earm, M. A. Knepper, and J. S. Han Antidiuretic Effect of Hydrochlorothiazide in Lithium-Induced Nephrogenic Diabetes Insipidus Is Associated with Upregulation of Aquaporin-2, Na-Cl Co-transporter, and Epithelial Sodium Channel J. Am. Soc. Nephrol., November 1, 2004; 15(11): 2836 - 2843. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Aviv, N. K. Hollenberg, and A. Weder Urinary Potassium Excretion and Sodium Sensitivity in Blacks Hypertension, April 1, 2004; 43(4): 707 - 713. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Nijenhuis, J. G.J. Hoenderop, and R. J.M. Bindels Downregulation of Ca2+ and Mg2+ Transport Proteins in the Kidney Explains Tacrolimus (FK506)-Induced Hypercalciuria and Hypomagnesemia J. Am. Soc. Nephrol., March 1, 2004; 15(3): 549 - 557. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Song, M. A. Knepper, J. G. Verbalis, and C. A. Ecelbarger Increased renal ENaC subunit and sodium transporter abundances in streptozotocin-induced type 1 diabetes Am J Physiol Renal Physiol, December 1, 2003; 285(6): F1125 - F1137. [Abstract] [Full Text] |
||||
![]() |
O. A. Weisz and J. P. Johnson Noncoordinate regulation of ENaC: paradigm lost? Am J Physiol Renal Physiol, November 1, 2003; 285(5): F833 - F842. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Lebowitz, B. An, R. S. Edinger, M. L. Zeidel, and J. P. Johnson Effect of altered Na+ entry on expression of apical and basolateral transport proteins in A6 epithelia Am J Physiol Renal Physiol, September 1, 2003; 285(3): F524 - F531. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |