Published online before print October 2, 2006, doi: 10.1161/01.HYP.0000244688.45472.95
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(Hypertension. 2006;48:892.)
© 2006 American Heart Association, Inc.
Original Articles |
ß-2 Adrenergic Receptor Diplotype Defines a Subset of Salt-Sensitive Hypertension
From the Division of Endocrinology, Diabetes, and Hypertension (L.P., N.S.K., J.S.W., G.H.W.), Division of Cardiology (T.S.P.), and Channing Laboratory (B.A.R.), Brigham and Women’s Hospital, and Harvard Medical School, Boston, Mass; Centre d’Investigation Clinique (X.J.), Departement de Genetique, Hôpital Européen Georges Pompidou, Paris, France; Departments of Medicine and Pharmacology (N.J.B.), Vanderbilt University Medical Center, Nashville, Tenn; and the Department of Medicine (P.N.H.), University of Utah School of Medicine, Salt Lake City.
Correspondence to Gordon H. Williams, Brigham and Women’s Hospital, Division of Endocrinology, Diabetes, and Hypertension, 221 Longwood Ave, Boston, MA 02115. E-mail gwilliams{at}partners.org
Two genetic variants of the ß-2 adrenergic receptor, 46G>A and 79C>G, affect agonist-mediated receptor downregulation and vascular reactivity. We determined whether these variants were associated with hypertension, per se, blood pressure response to dietary sodium, 2 forms of salt-sensitive hypertension (low renin and nonmodulation), and the activity of the renin–angiotensin–aldosterone system. Included are 280 hypertensive and 65 normotensive white subjects who had the 2 ß-2 adrenergic receptor genotypes available. Of all subjects, 171 hypertensive and 48 normotensive subjects had complete data for intermediate phenotyping and blood pressure evaluation on high- and low-sodium balance. The ß-2 adrenergic receptor variants were not associated with hypertension per se. However, among hypertensive subjects, the change (from low to high sodium balance) in mean arterial pressure differed significantly by genotype and by diplotype. Compared with all of the other diplotypes combined, 46AA/79CC was associated with a greater change in blood pressure. Furthermore, this diplotype was associated with low-renin (LR) hypertension (identifying 32% of the LR hypertensives), higher plasma aldosterone, and lower plasma renin and serum potassium levels. In conclusion, the 46AA/79CC diplotype is associated with greater blood pressure response to dietary sodium and higher odds of LR hypertension. We propose that the mechanism for the observed association is inadequate suppression of aldosterone with salt intake, implicating the ß-2 adrenergic receptor in the regulation of aldosterone secretion. This hypothesis was confirmed in isolated glomerulosa cells, where ß-2 adrenergic receptor stimulation increased aldosterone secretion, whereas blockade reduced the stimulated aldosterone response. Importantly, this association could only be detected with an intermediate and not a distant phenotype.
Key Words: ß-2 adrenergic receptor • hypertension • salt-sensitive hypertension • low-renin hypertension • single nucleotide polymorphisms • haplotypes • diplotypes
Related Article:
Hypertension 2006 48: 820-821.
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