| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
INVITED REVIEW
CALL FOR PAPERS
Molecular Mechanisms Linking Salt to Hypertension
Departments of 1Physiology and 2Medicine and 3Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Maryland School of Medicine; and 4Division of Endocrinology, Department of Medicine, Baltimore Veterans Affairs Medical Center and University of Maryland School of Medicine, Baltimore, Maryland
A critical question in hypertension research is: How is long-term blood pressure controlled? Excessive NaCl ingestion or NaCl retention by the kidneys and the consequent tendency toward plasma volume expansion lead to hypertension. Nevertheless, the precise mechanisms linking salt to high blood pressure are unresolved. The discovery of endogenous ouabain, an adrenocortical hormone, provided an important clue. Ouabain, a selective Na+ pump inhibitor, has cardiotonic and vasotonic effects. Plasma endogenous ouabain levels are significantly elevated in 
40% of patients with essential hypertension and in animals with several forms of salt-dependent hypertension. Also, prolonged ouabain administration induces hypertension in rodents. Mice with mutant Na+ pumps or Na/Ca exchangers (NCX) and studies with a ouabain antagonist and an NCX blocker are revealing the missing molecular mechanisms. These data demonstrate that 
2 Na+ pumps and NCX1 participate in long-term regulation of vascular tone and blood pressure. Pharmacological agents or mutations in the 2 Na+ pump that interfere with the action of ouabain on the pump, and reduced NCX1 expression or agents that block NCX all impede the development of salt-dependent or ouabain-induced hypertension. Conversely, nanomolar ouabain, reduced 2 Na+ pump expression, and smooth muscle-specific overexpression of NCX1 all induce hypertension. Furthermore, ouabain and reduced 2 Na+ pump expression increase myogenic tone in isolated mesenteric small arteries in vitro, thereby tying these effects directly to the elevation of blood pressure. Thus, endogenous ouabain, and vascular 2 Na+ pumps and NCX1, are critical links between salt and hypertension. New pharmacological agents that act on these molecular links have potential in the clinical management of hypertension.
ouabain; Na+ pump; Na/Ca exchanger; Ca2+; myogenic tone
This article has been cited by other articles:
|
|
 |
|
  B. A. Bart Treatment of Congestion in Congestive Heart Failure: Ultrafiltration Is the Only Rational Initial Treatment of Volume Overload in Decompensated Heart Failure Circ Heart Fail, September 1, 2009; 2(5): 499 - 504. [Full Text] [PDF]
|
|
|
|
 |
|
 E. Pimenta, K. K. Gaddam, S. Oparil, I. Aban, S. Husain, L. J. Dell'Italia, and D. A. Calhoun Effects of Dietary Sodium Reduction on Blood Pressure in Subjects With Resistant Hypertension: Results From a Randomized Trial Hypertension, September 1, 2009; 54(3): 475 - 481. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Cao, K. Payne, W. Lee-Kwon, Z. Zhang, S. W. Lim, J. Hamlyn, M. P. Blaustein, H. M. Kwon, and T. L. Pallone Chronic ouabain treatment induces vasa recta endothelial dysfunction in the rat Am J Physiol Renal Physiol, January 1, 2009; 296(1): F98 - F106. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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 Sodium-, potassium-, chloride-, and bicarbonate-related effects on blood pressure and electrolyte homeostasis in deoxycorticosterone acetate-treated rats Am J Physiol Renal Physiol, December 1, 2008; 295(6): F1752 - F1763. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. L. Loreaux, B. Kaul, J. N. Lorenz, and J. B. Lingrel Ouabain-Sensitive {alpha}1 Na,K-ATPase Enhances Natriuretic Response to Saline Load J. Am. Soc. Nephrol., October 1, 2008; 19(10): 1947 - 1954. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Kaplan A Natriuretic Hormone-Binding Site on the Sodium Pump J. Am. Soc. Nephrol., October 1, 2008; 19(10): 1839 - 1840. [Full Text] [PDF]
|
|
|
|
|
|
A. Edwards and T. L. Pallone Mechanisms underlying angiotensin II-induced calcium oscillations Am J Physiol Renal Physiol, August 1, 2008; 295(2): F568 - F584. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Mandal, N. A. Delamere, and M. Shahidullah Ouabain-induced stimulation of sodium-hydrogen exchange in rat optic nerve astrocytes Am J Physiol Cell Physiol, July 1, 2008; 295(1): C100 - C110. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. R. Olson and T. M. Hoagland Effects of freshwater and saltwater adaptation and dietary salt on fluid compartments, blood pressure, and venous capacitance in trout Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2008; 294(3): R1061 - R1067. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Zhang, C. Cao, Z. Zhang, W. G. Wier, A. Edwards, and T. L. Pallone Membrane current oscillations in descending vasa recta pericytes Am J Physiol Renal Physiol, March 1, 2008; 294(3): F656 - F666. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Thifault, S. Ondrej, Y. Sun, A. Fortin, E. Skamene, R. Lalonde, J. Tremblay, and P. Hamet Genetic determinants of emotionality and stress response in AcB/BcA recombinant congenic mice and in silico evidence of convergence with cardiovascular candidate genes Hum. Mol. Genet., February 1, 2008; 17(3): 331 - 344. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Hirota and L. J. Janssen Sodium and asthma: something borrowed, something new? Am J Physiol Lung Cell Mol Physiol, December 1, 2007; 293(6): L1369 - L1373. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. P. Blaustein and W. G. Wier Local Sodium, Global Reach: Filling the Gap Between Salt and Hypertension Circ. Res., November 9, 2007; 101(10): 959 - 961. [Full Text] [PDF]
|
|
|
|
|
|
A. Edwards and T. L. Pallone Ouabain modulation of cellular calcium stores and signaling Am J Physiol Renal Physiol, November 1, 2007; 293(5): F1518 - F1532. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. N. Orlov and A. A. Mongin Salt-sensing mechanisms in blood pressure regulation and hypertension Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2039 - H2053. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Feldmann, V. Glukmann, E. Medvenev, U. Shpolansky, D. Galili, D. Lichtstein, and H. Rosen Role of endosomal Na+-K+-ATPase and cardiac steroids in the regulation of endocytosis Am J Physiol Cell Physiol, September 1, 2007; 293(3): C885 - C896. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Chen, T. W. Moon, K. R. Olson, R. A. Dombkowski, and S. F. Perry The effects of salt-induced hypertension on {alpha}1-adrenoreceptor expression and cardiovascular physiology in the rainbow trout (Oncorhynchus mykiss) Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2007; 293(3): R1384 - R1392. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Schoner and G. Scheiner-Bobis Endogenous and exogenous cardiac glycosides: their roles in hypertension, salt metabolism, and cell growth Am J Physiol Cell Physiol, August 1, 2007; 293(2): C509 - C536. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Pritchard, M. Parvatiyar, D. P. Bullard, R. M. Lynch, J. N. Lorenz, and R. J. Paul Transgenic mice expressing Na+-K+-ATPase in smooth muscle decreases blood pressure Am J Physiol Heart Circ Physiol, August 1, 2007; 293(2): H1172 - H1182. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Edwards and T. L. Pallone Modification of cytosolic calcium signaling by subplasmalemmal microdomains Am J Physiol Renal Physiol, June 1, 2007; 292(6): F1827 - F1845. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. J. Adrogue and N. E. Madias Sodium and Potassium in the Pathogenesis of Hypertension N. Engl. J. Med., May 10, 2007; 356(19): 1966 - 1978. [Full Text] [PDF]
|
|
|
|
|
|
J. N. Lorenz, I. Dostanic-Larson, G. E. Shull, and J. B. Lingrel Ouabain Inhibits Tubuloglomerular Feedback in Mutant Mice with Ouabain-Sensitive {alpha}1 Na,K-ATPase J. Am. Soc. Nephrol., September 1, 2006; 17(9): 2457 - 2463. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
