Impaired endothelium-dependent flow-mediated vasodilation in hypertensive subjects with hyperaldosteronism

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 center dot mL(-1) center dot h(-1), urinary aldosterone >12 mug/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.