Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

PNAS 104 (41): 16281-16286

Copyright © 2007 by the National Academy of Sciences.

BIOLOGICAL SCIENCES / MEDICAL SCIENCES

Plasma sodium stiffens vascular endothelium and reduces nitric oxide release

Hans Oberleithner*,{dagger}, Christoph Riethmüller*, Hermann Schillers*, Graham A. MacGregor{ddagger}, Hugh E. de Wardener{ddagger}, and Martin Hausberg§

*Institute of Physiology II and §Department of Internal Medicine D, University of Münster, 48149 Münster, Germany; and {ddagger}Blood Pressure Unit, Department of Cardiac and Vascular Medicine, St. George's University of London, London SW17 ORE, United Kingdom

Communicated by Gerhard Giebisch, Yale University School of Medicine, New Haven, CT, August 21, 2007

Received for publication February 16, 2007.

Abstract: Dietary salt plays a major role in the regulation of blood pressure, and the mineralocorticoid hormone aldosterone controls salt homeostasis and extracellular volume. Recent observations suggest that a small increase in plasma sodium concentration may contribute to the pressor response of dietary salt. Because endothelial cells are (i) sensitive to aldosterone, (ii) in physical contact with plasma sodium, and (iii) crucial regulators of vascular tone, we tested whether acute changes in plasma sodium concentration, within the physiological range, can alter the physical properties of endothelial cells. The tip of an atomic force microscope was used as a nanosensor to measure stiffness of living endothelial cells incubated for 3 days in a culture medium containing aldosterone at a physiological concentration (0.45 nM). Endothelial cell stiffness was unaffected by acute changes in sodium concentration <135 mM but rose steeply between 135 and 145 mM. The increase in stiffness occurred within minutes. Lack of aldosterone in the culture medium or treatment with the epithelial sodium channel inhibitor amiloride prevented this response. Nitric oxide formation was found down-regulated in cells cultured in aldosterone-containing high sodium medium. The results suggest that changes in plasma sodium concentration per se may affect endothelial function and thus control vascular tone.

Key Words: atomic force microscopy • cell stiffness • endothelial dysfunction • eplerenone

Freely available online through the PNAS open access option.

Author contributions: H.O., C.R., H.S., G.A.M., H.E.d.W., and M.H. designed research; H.O. performed research; H.O. analyzed data; and H.O. wrote the paper.

The authors declare no conflict of interest.

{dagger}To whom correspondence should be addressed. E-mail: oberlei{at}uni-muenster.de

© 2007 by The National Academy of Sciences of the USA

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Dietary sodium loading impairs microvascular function independent of blood pressure in humans: role of oxidative stress.
J. L. Greaney, J. J. DuPont, S. L. Lennon-Edwards, P. W. Sanders, D. G. Edwards, and W. B. Farquhar (2012)
J. Physiol. 590, 5519-5528
   Abstract »    Full Text »    PDF »
Failure to Downregulate the Epithelial Sodium Channel Causes Salt Sensitivity in Hsd11b2 Heterozygote Mice.
E. Craigie, L. C. Evans, J. J. Mullins, and M. A. Bailey (2012)
Hypertension 60, 684-690
   Abstract »    Full Text »    PDF »
Serum phosphorus as a predictor of low-grade albuminuria in a general population without evidence of chronic kidney disease.
H. Lee, S. W. Oh, N. J. Heo, H. J. Chin, K. Y. Na, S. Kim, and D.-W. Chae (2012)
Nephrol. Dial. Transplant. 27, 2799-2806
   Abstract »    Full Text »    PDF »
The role of oxysterols in control of endothelial stiffness.
T. P. Shentu, D. K. Singh, M.-J. Oh, S. Sun, L. Sadaat, A. Makino, T. Mazzone, P. V. Subbaiah, M. Cho, and I. Levitan (2012)
J. Lipid Res. 53, 1348-1358
   Abstract »    Full Text »    PDF »
Aldosterone and parathyroid hormone: a precarious couple for cardiovascular disease.
A. Tomaschitz, E. Ritz, B. Pieske, A. Fahrleitner-Pammer, K. Kienreich, J. H. Horina, C. Drechsler, W. Marz, M. Ofner, T. R. Pieber, et al. (2012)
Cardiovasc Res 94, 10-19
   Abstract »    Full Text »    PDF »
Intradialytic Hypertension and its Association with Endothelial Cell Dysfunction.
J. K. Inrig, P. Van Buren, C. Kim, W. Vongpatanasin, T. J. Povsic, and R. D. Toto (2011)
Clin. J. Am. Soc. Nephrol. 6, 2016-2024
   Abstract »    Full Text »    PDF »
Intradermal microdialysis of hypertonic saline attenuates cutaneous vasodilatation in response to local heating.
J. J. DuPont, W. B. Farquhar, and D. G. Edwards (2011)
Exp Physiol 96, 674-680
   Abstract »    Full Text »    PDF »
Pre-clinical data on the role of mineralocorticoid receptor antagonists in reversing vascular inflammation.
S. Yagi and M. Sata (2011)
Eur. Heart J. Suppl. 13, B15-B20
   Abstract »    Full Text »    PDF »
Membrane potential depolarization decreases the stiffness of vascular endothelial cells.
C. Callies, J. Fels, I. Liashkovich, K. Kliche, P. Jeggle, K. Kusche-Vihrog, and H. Oberleithner (2011)
J. Cell Sci. 124, 1936-1942
   Abstract »    Full Text »    PDF »
ACCF/AHA 2011 Expert Consensus Document on Hypertension in the Elderly: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents.
W. S. Aronow, J. L. Fleg, C. J. Pepine, N. T. Artinian, G. Bakris, A. S. Brown, K. C. Ferdinand, M. A. Forciea, W. H. Frishman, C. Jaigobin, et al. (2011)
Circulation 123, 2434-2506
   Full Text »    PDF »
Endothelial function is impaired after a high-salt meal in healthy subjects.
K. M. Dickinson, P. M. Clifton, and J. B. Keogh (2011)
Am J Clin Nutr 93, 500-505
   Abstract »    Full Text »    PDF »
C-Reactive Protein Makes Human Endothelium Stiff and Tight.
K. Kusche-Vihrog, K. Urbanova, A. Blanque, M. Wilhelmi, H. Schillers, K. Kliche, H. Pavenstadt, E. Brand, and H. Oberleithner (2011)
Hypertension 57, 231-237
   Abstract »    Full Text »    PDF »
Republished paper: Arterial stiffness in chronic kidney disease: causes and consequences.
C. D. Chue, J. N. Townend, R. P. Steeds, and C. J. Ferro (2010)
Postgrad. Med. J. 86, 560-566
   Abstract »    Full Text »    PDF »
oxLDL-induced decrease in lipid order of membrane domains is inversely correlated with endothelial stiffness and network formation.
T. P. Shentu, I. Titushkin, D. K. Singh, K. J. Gooch, P. V. Subbaiah, M. Cho, and I. Levitan (2010)
Am J Physiol Cell Physiol 299, C218-C229
   Abstract »    Full Text »    PDF »
Effect of Modest Salt Reduction on Skin Capillary Rarefaction in White, Black, and Asian Individuals With Mild Hypertension.
F. J. He, M. Marciniak, N. D. Markandu, T. F. Antonios, and G. A. MacGregor (2010)
Hypertension 56, 253-259
   Abstract »    Full Text »    PDF »
Arterial stiffness in chronic kidney disease: causes and consequences.
C. D. Chue, J. N. Townend, R. P. Steeds, and C. J. Ferro (2010)
Heart 96, 817-823
   Abstract »    Full Text »    PDF »
Plasma aldosterone levels are associated with increased cardiovascular mortality: the Ludwigshafen Risk and Cardiovascular Health (LURIC) study.
A. Tomaschitz, S. Pilz, E. Ritz, A. Meinitzer, B. O. Boehm, and W. Marz (2010)
Eur. Heart J. 31, 1237-1247
   Abstract »    Full Text »    PDF »
Cardiovascular Problems on Hemodialysis: Current Deficits and Potential Improvement.
E. Ritz and J. Bommer (2009)
Clin. J. Am. Soc. Nephrol. 4, S71-S78
   Abstract »    Full Text »    PDF »
Left Ventricular Mass in Chronic Kidney Disease and ESRD.
R. J. Glassock, R. Pecoits-Filho, and S. H. Barberato (2009)
Clin. J. Am. Soc. Nephrol. 4, S79-S91
   Abstract »    Full Text »    PDF »
Low dietary sodium intake is associated with enhanced vascular endothelial function in middle-aged and older adults with elevated systolic blood pressure.
K. L. Jablonski, P. E. Gates, G. L. Pierce, and D. R. Seals (2009)
Therapeutic Advances in Cardiovascular Disease 3, 347-356
   Abstract »    PDF »
The Soluble VEGF Receptor sFlt1 Contributes to Endothelial Dysfunction in CKD.
G. S. D. Marco, S. Reuter, U. Hillebrand, S. Amler, M. Konig, E. Larger, H. Oberleithner, E. Brand, H. Pavenstadt, and M. Brand (2009)
J. Am. Soc. Nephrol. 20, 2235-2245
   Abstract »    Full Text »    PDF »
Aldosterone, a vasculotoxic agent--novel functions for an old hormone.
E. Ritz and A. Tomaschitz (2009)
Nephrol. Dial. Transplant. 24, 2302-2305
   Full Text »    PDF »
Vascular consequences of dietary salt intake.
P. W. Sanders (2009)
Am J Physiol Renal Physiol 297, F237-F243
   Abstract »    Full Text »    PDF »
Sodium Intake and Vascular Stiffness in Hypertension.
M. E. Safar, M. Temmar, A. Kakou, P. Lacolley, and S. N. Thornton (2009)
Hypertension 54, 203-209
   Full Text »    PDF »
Endothelial Epithelial Sodium Channel Inhibition Activates Endothelial Nitric Oxide Synthase via Phosphoinositide 3-Kinase/Akt in Small-Diameter Mesenteric Arteries.
F. R. Perez, F. Venegas, M. Gonzalez, S. Andres, C. Vallejos, G. Riquelme, J. Sierralta, and L. Michea (2009)
Hypertension 53, 1000-1007
   Abstract »    Full Text »    PDF »
How Little Aldosterone is Able to Raise Blood Pressure?.
E. Ritz (2009)
Clin. J. Am. Soc. Nephrol. 4, 703-710
   Full Text »    PDF »
Hypertension in mice lacking the CXCR3 chemokine receptor.
H.-H. Hsu, K. Duning, H. H. Meyer, M. Stolting, T. Weide, S. Kreusser, T. van Le, C. Gerard, R. Telgmann, S.-M. Brand-Herrmann, et al. (2009)
Am J Physiol Renal Physiol 296, F780-F789
   Abstract »    Full Text »    PDF »
Salt Inactivates Endothelial Nitric Oxide Synthase in Endothelial Cells.
J. Li, J. White, L. Guo, X. Zhao, J. Wang, E. J. Smart, and X.-A. Li (2009)
J. Nutr. 139, 447-451
   Abstract »    Full Text »    PDF »
Potassium softens vascular endothelium and increases nitric oxide release.
H. Oberleithner, C. Callies, K. Kusche-Vihrog, H. Schillers, V. Shahin, C. Riethmuller, G. A. MacGregor, and H. E. de Wardener (2009)
PNAS 106, 2829-2834
   Abstract »    Full Text »    PDF »
Sodium-, potassium-, chloride-, and bicarbonate-related effects on blood pressure and electrolyte homeostasis in deoxycorticosterone acetate-treated rats.
A. Ziomber, A. Machnik, A. Dahlmann, P. Dietsch, F.-X. Beck, H. Wagner, K. F. Hilgers, F. C. Luft, K.-U. Eckardt, and J. Titze (2008)
Am J Physiol Renal Physiol 295, F1752-F1763
   Abstract »    Full Text »    PDF »
Apoptosis leads to a degradation of vital components of active nuclear transport and a dissociation of the nuclear lamina.
A. Kramer, I. Liashkovich, H. Oberleithner, S. Ludwig, I. Mazur, and V. Shahin (2008)
PNAS 105, 11236-11241
   Abstract »    Full Text »    PDF »
Increased inorganic phosphate induces human endothelial cell apoptosis in vitro.
G. S. Di Marco, M. Hausberg, U. Hillebrand, P. Rustemeyer, W. Wittkowski, D. Lang, and H. Pavenstadt (2008)
Am J Physiol Renal Physiol 294, F1381-F1387
   Abstract »    Full Text »    PDF »
Environmental Smoke Exposure: A Complex Cardiovascular Challenge.
M. Hausberg and V. K. Somers (2008)
Hypertension 51, 1468-1469
   Full Text »    PDF »
Revisiting the Dialysate Sodium Prescription as a Tool for Better Blood Pressure and Interdialytic Weight Gain Management in Hemodialysis Patients.
S. F. F. Santos and A. J. Peixoto (2008)
Clin. J. Am. Soc. Nephrol. 3, 522-530
   Abstract »    Full Text »    PDF »
Aldosterone and Vascular Inflammation.
N. J. Brown (2008)
Hypertension 51, 161-167
   Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882