doi: 10.1161/hy02t2.102959
(Hypertension. 2002;39:470.)
© 2002 American Heart Association, Inc.
Scientific Contributions |
Targeted Proteomic Profiling of Renal Na+ Transporter and Channel Abundances in Angiotensin II Type 1a Receptor Knockout Mice
From the Laboratory of Kidney and Electrolyte Metabolism (H.L.B., K.T.B., M.A.K.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md, and the Department of Medicine (A.J.A., T.M.C.), Duke University, Durham, NC.
Correspondence to Mark A. Knepper, MD, PhD, Building 10, Room 6N260, 10 Center Dr, MSC-1603, National Institutes of Health, Bethesda, MD 20892-1603. E-mail knep{at}helix.nih.gov
The renal tubule transporters responsible for Na+ and water transport along the nephron have been identified and cloned, permitting comprehensive analysis of transporter protein abundance changes in complex physiological models by using a "targeted proteomics" approach. Here, we apply this approach to screen renal homogenates from mice in which the gene for the angiotensin II type 1a (AT1a) receptor has been deleted (versus wild-type mice) to determine which sodium transporters and channels are regulated by the AT1a receptor at the protein abundance level. In mice maintained on a low NaCl diet (<0.02% NaCl), (1) the abundances of 2 aldosterone-regulated transporters were markedly decreased in knockout versus wild-type mice, namely, the thiazide-sensitive cotransporter and the 
-subunit of the amiloride-sensitive Na+ channel (-ENaC); (2) the abundances of ß-ENaC and 
-ENaC were markedly increased; and (3) there were no significant changes in the abundances of the proximal tubule Na+-H+ exchanger or the Na+-K+-2Cl- cotransporter of the thick ascending limb. When the experiment was repeated on higher NaCl diets (0.4% or 6% NaCl), the decrease in -ENaC abundance persisted, whereas the other changes were abolished. Analysis of serum aldosterone concentration in AT1a knockout mice and wild-type mice on the low NaCl diet revealed the absence of a decrease with AT1a gene deletion (11.8±2.3 nmol/L for knockout mice and 5.7±0.8 nmol/L for wild-type mice [significantly increased]). These results reveal that the AT1a receptor plays an important role in regulation of Na+ transporter and channel proteins in the "post-macula densa" region of the renal tubule via a mechanism that is not dependent on altered circulating aldosterone concentrations.
Key Words: sodium • angiotensin II • receptors, angiotensin II • kidney • mice
This article has been cited by other articles:
 |
|
 |
|
  V. K. Madala Halagappa, S. Tiwari, S. Riazi, X. Hu, and C. M. Ecelbarger Chronic candesartan alters expression and activity of NKCC2, NCC, and ENaC in the obese Zucker rat Am J Physiol Renal Physiol, May 1, 2008; 294(5): F1222 - F1231. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Fenton and M. A. Knepper Mouse Models and the Urinary Concentrating Mechanism in the New Millennium Physiol Rev, October 1, 2007; 87(4): 1083 - 1112. [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]
|
|
|
|
 |
|
 H. Kobori, M. Nangaku, L. G. Navar, and A. Nishiyama The Intrarenal Renin-Angiotensin System: From Physiology to the Pathobiology of Hypertension and Kidney Disease Pharmacol. Rev., September 1, 2007; 59(3): 251 - 287. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Verlander The thiazide-sensitive NaCl cotransporter: a new target for acute regulation of salt and water transport by angiotensin II Am J Physiol Renal Physiol, September 1, 2007; 293(3): F660 - F661. [Full Text] [PDF]
|
|
|
|
|
|
R. M. Ortiz, M. L. Graciano, D. Seth, M. S. Awayda, and L. G. Navar Aldosterone receptor antagonism exacerbates intrarenal angiotensin II augmentation in ANG II-dependent hypertension Am J Physiol Renal Physiol, July 1, 2007; 293(1): F139 - F147. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L Zhuo and X. C Li Review: Novel roles of intracrine angiotensin II and signalling mechanisms in kidney cells Journal of Renin-Angiotensin-Aldosterone System, March 1, 2007; 8(1): 23 - 33. [Abstract] [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]
|
|
|
|
|
|
J. Nielsen, T.-H. Kwon, J. Frokiaer, M. A. Knepper, and S. Nielsen Maintained ENaC trafficking in aldosterone-infused rats during mineralocorticoid and glucocorticoid receptor blockade Am J Physiol Renal Physiol, January 1, 2007; 292(1): F382 - F394. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Wall, M. A. Knepper, K. A. Hassell, M. P. Fischer, A. Shodeinde, W. Shin, T. D. Pham, J. W. Meyer, J. N. Lorenz, W. H. Beierwaltes, et al. Hypotension in NKCC1 null mice: role of the kidneys Am J Physiol Renal Physiol, February 1, 2006; 290(2): F409 - F416. [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. Takahashi, M. L. S. S. Lopez, J. E. Cowhig Jr., M. A. Taylor, T. Hatada, E. Riggs, G. Lee, R. A. Gomez, H.-S. Kim, and O. Smithies Ren1c Homozygous Null Mice Are Hypotensive and Polyuric, but Heterozygotes Are Indistinguishable from Wild-Type J. Am. Soc. Nephrol., January 1, 2005; 16(1): 125 - 132. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Maruvada and S. Srivastava Biomarkers for Cancer Diagnosis: Implications for Nutritional Research J. Nutr., June 1, 2004; 134(6): 1640S - 1645S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
S. M. Wall, M. P. Fischer, D. M. Glapion, and M. De La Calzada ANG II reduces net acid secretion in rat outer medullary collecting duct Am J Physiol Renal Physiol, November 1, 2003; 285(5): F930 - F937. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-H. Kwon, J. Nielsen, Y.-H. Kim, M. A. Knepper, J. Frokiaer, and S. Nielsen Regulation of sodium transporters in the thick ascending limb of rat kidney: response to angiotensin II Am J Physiol Renal Physiol, July 1, 2003; 285(1): F152 - F165. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. T. Beutler, S. Masilamani, S. Turban, J. Nielsen, H. L. Brooks, S. Ageloff, R. A. Fenton, R. K. Packer, and M. A. Knepper Long-Term Regulation of ENaC Expression in Kidney by Angiotensin II Hypertension, May 1, 2003; 41(5): 1143 - 1150. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Loffing and B. Kaissling Sodium and calcium transport pathways along the mammalian distal nephron: from rabbit to human Am J Physiol Renal Physiol, April 1, 2003; 284(4): F628 - F643. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Masilamani, X. Wang, G.-H. Kim, H. Brooks, J. Nielsen, S. Nielsen, K. Nakamura, J. B. Stokes, and M. A. Knepper Time course of renal Na-K-ATPase, NHE3, NKCC2, NCC, and ENaC abundance changes with dietary NaCl restriction Am J Physiol Renal Physiol, October 1, 2002; 283(4): F648 - F657. [Abstract] [Full Text] [PDF]
|
|