Published Online
on June 1, 2004

A more recent version of this article appeared on June 15, 2004

This Article Full Text (PDF) All Versions of this Article: 109/23/2857    most recent 01.CIR.0000129307.26791.8Ev1 Alert me when this article is cited Alert me if a correction is posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nishizaka, M. K. Articles by Calhoun, D. A. Search for Related Content PubMed PubMed Citation Articles by Nishizaka, M. K. Articles by Calhoun, D. A. Related Collections Clinical Studies

Submitted on July 28, 2003
Revised on February 19, 2004
Accepted on February 25, 2004

Impaired Endothelium-Dependent Flow-Mediated Vasodilation in Hypertensive Subjects With Hyperaldosteronism

Mari K. Nishizaka MD^*, M. Amin Zaman MD, Sharon A. Green RN, Kerry Y. Renfroe RN, and David A. Calhoun MD

From the Vascular Biology and Hypertension Program, University of Alabama at Birmingham, Birmingham.

^* To whom correspondence should be addressed. E-mail: marikn{at}uab.edu.

Background--Recent studies suggest that aldosterone may impair endothelium-dependent vascular function through suppression of nitric oxide formation. Assessments of forearm blood flow or arterial compliance suggest a similar effect in humans. The present study was designed to determine whether chronic aldosterone excess in subjects with resistant hypertension impairs endothelium-dependent vascular reactivity as indexed by direct assessment of brachial artery flow-mediated dilation (FMD).

Methods and Results--Consecutive subjects (n=80) with resistant hypertension were prospectively evaluated with an early-morning ratio of plasma aldosterone to plasma renin activity and 24-hour urinary aldosterone and sodium. Changes in brachial artery diameter during reactive hyperemia were measured by high-resolution ultrasound. Hyperaldosteronism was diagnosed on the basis of a renin activity <1.0 ng · mL^-1 · h^-1, urinary aldosterone >12 µg/24 h, and urinary sodium >200 mEq/24 h. FMD was significantly lower in 36 subjects with hyperaldosteronism (1.8±1.3% versus 3.9±1.9% from baseline; P<0.0001) compared with the 44 subjects without hyperaldosteronism. FMD was negatively and significantly correlated with plasma aldosterone (r=-0.38, P=0.0006), 24-hour urinary aldosterone (r=-0.49, P<0.0001), and ratio of plasma aldosterone to plasma renin activity (r=-0.43, P<0.0001) but was independent of blood pressure, age, and body mass index. In 30 subjects, 3 months of treatment with spironolactone significantly increased FMD (2.5±1.7 versus 6.0±2.0%; P<0.0001) independently of blood pressure change.

Conclusions--These data demonstrate a strong association between aldosterone excess and impaired endothelial function in human subjects as indexed by flow-mediated arterial vasodilation. These results suggest that chronic aldosteronism may have a blood pressure-independent effect on cardiovascular disease progression in subjects with resistant hypertension.

Key words: aldosterone • hypertension • renin • ultrasonics • vasodilation

This article has been cited by other articles:

				A. Tasatargil, M. Tekcan, C. Celik-Ozenci, N. Ece Gungor, and B. Dalkiran Aldosterone-induced endothelial dysfunction of rat aorta: role of poly(ADP-ribose) activation Journal of Renin-Angiotensin-Aldosterone System, September 1, 2009; 10(3): 127 - 137. [Abstract] [PDF]

				E. Ritz How Little Aldosterone is Able to Raise Blood Pressure? Clin. J. Am. Soc. Nephrol., April 1, 2009; 4(4): 703 - 710. [Full Text] [PDF]

				H. Oberleithner, C. Riethmuller, H. Schillers, G. A. MacGregor, H. E. de Wardener, and M. Hausberg Plasma sodium stiffens vascular endothelium and reduces nitric oxide release PNAS, October 9, 2007; 104(41): 16281 - 16286. [Abstract] [Full Text] [PDF]

				S. J. Hood, K. P. Taylor, M. J. Ashby, and M. J. Brown The Spironolactone, Amiloride, Losartan, and Thiazide (SALT) Double-Blind Crossover Trial in Patients With Low-Renin Hypertension and Elevated Aldosterone-Renin Ratio Circulation, July 17, 2007; 116(3): 268 - 275. [Abstract] [Full Text] [PDF]

				F. Nietlispach, B. Julius, R. Schindler, A. Bernheim, C. Binkert, W. Kiowski, and H. P. Brunner-La Rocca Influence of Acute and Chronic Mineralocorticoid Excess on Endothelial Function in Healthy Men Hypertension, July 1, 2007; 50(1): 82 - 88. [Abstract] [Full Text] [PDF]

				A. Kazory and I. David Weiner Primary hyperaldosteronism in a patient with end-stage renal disease Nephrol. Dial. Transplant., November 24, 2006; (2006) gfl702v1. [Full Text] [PDF]

				G. P. Rossi, G. Bernini, G. Desideri, B. Fabris, C. Ferri, G. Giacchetti, C. Letizia, M. Maccario, M. Mannelli, M.-J. Matterello, et al. Renal Damage in Primary Aldosteronism: Results of the PAPY Study Hypertension, August 1, 2006; 48(2): 232 - 238. [Abstract] [Full Text] [PDF]

				T. A. Williams, A. Verhovez, A. Milan, F. Veglio, and P. Mulatero Protective Effect of Spironolactone on Endothelial Cell Apoptosis Endocrinology, May 1, 2006; 147(5): 2496 - 2505. [Abstract] [Full Text] [PDF]

				T.-Y. Chun and J. H. Pratt Nongenomic Renal Effects of Aldosterone: Dependency on NO and Genomic Actions Hypertension, April 1, 2006; 47(4): 636 - 637. [Full Text] [PDF]

				J. Nehme, N. Mercier, C. Labat, A. Benetos, M. E Safar, C. Delcayre, and P. Lacolley Differences Between Cardiac and Arterial Fibrosis and Stiffness in Aldosterone-Salt Rats: Effect of Eplerenone Journal of Renin-Angiotensin-Aldosterone System, March 1, 2006; 7(1): 31 - 39. [Abstract] [PDF]

				S. Kathiresan, P. Gona, M. G. Larson, J. A. Vita, G. F. Mitchell, G. H. Tofler, D. Levy, C. Newton-Cheh, T. J. Wang, E. J. Benjamin, et al. Cross-Sectional Relations of Multiple Biomarkers From Distinct Biological Pathways to Brachial Artery Endothelial Function Circulation, February 21, 2006; 113(7): 938 - 945. [Abstract] [Full Text] [PDF]

				J. W. Funder Relative Aldosterone Excess: Relative to What? Hypertension, October 1, 2005; 46(4): 643 - 644. [Full Text] [PDF]

				S. J. Duffy, E. S. Biegelsen, R. T. Eberhardt, D. F. Kahn, B. A. Kingwell, and J. A. Vita Low-Renin Hypertension With Relative Aldosterone Excess Is Associated With Impaired NO-Mediated Vasodilation Hypertension, October 1, 2005; 46(4): 707 - 713. [Abstract] [Full Text] [PDF]

				C. Saha, G. J. Eckert, W. T. Ambrosius, T.-Y. Chun, M. A. Wagner, Q. Zhao, and J. H. Pratt Improvement in Blood Pressure With Inhibition of the Epithelial Sodium Channel in Blacks With Hypertension Hypertension, September 1, 2005; 46(3): 481 - 487. [Abstract] [Full Text] [PDF]

				D. G. Warnock and P. D. Bell Improvement of Blood Pressure With Inhibition of the Epithelial Sodium Channel in Blacks With Hypertension Hypertension, September 1, 2005; 46(3): 469 - 470. [Full Text] [PDF]

				J. Blanco-Rivero, V. Cachofeiro, V. Lahera, R. Aras-Lopez, I. Marquez-Rodas, M. Salaices, F. E. Xavier, M. Ferrer, and G. Balfagon Participation of Prostacyclin in Endothelial Dysfunction Induced by Aldosterone in Normotensive and Hypertensive Rats Hypertension, July 1, 2005; 46(1): 107 - 112. [Abstract] [Full Text] [PDF]