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).


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.
Nishizaka
Mari K
MK
Vascular Biology and Hypertension Program, University of Alabama at Birmingham, Birmingham, USA. marikn@uab.edu
Zaman
M Amin
MA
Green
Sharon A
SA
Renfroe
Kerry Y
KY
Calhoun
David A
DA
D000328:Adult; D000450:Aldosterone / Q000652:urine; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D018056:Hemorheology; D006801:Humans; D006929:Hyperaldosteronism / Q000150:complications / Q000503:physiopathology*; D006940:Hyperemia / Q000503:physiopathology; D006973:Hypertension / Q000150:complications / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012083:Renin / Q000097:blood; D012964:Sodium / Q000652:urine; D014463:Ultrasonography; D014664:Vasodilation / Q000502:physiology*
D000450:Aldosterone; D012964:Sodium; D012083:Renin