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 x mL(-1) x h(-1), urinary aldosterone >12 microg/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.