on June 1, 2004
Published online before print June 1, 2004, doi: 10.1161/01.CIR.0000129307.26791.8E
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Submitted on July 28, 2003
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.
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*,
Key words: aldosterone • hypertension • renin • ultrasonics • vasodilation
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