| Beta-2 adrenergic receptor diplotype defines a subset of salt-sensitive hypertension. | |
| | |
MedLine Citation:
|
PMID: 17015767 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Two genetic variants of the beta-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 beta-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 beta-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 beta-2 adrenergic receptor in the regulation of aldosterone secretion. This hypothesis was confirmed in isolated glomerulosa cells, where beta-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. |
| | |
Authors:
|
Luminita Pojoga; Nikheel S Kolatkar; Jonathan S Williams; Todd S Perlstein; Xavier Jeunemaitre; Nancy J Brown; Paul N Hopkins; Benjamin A Raby; Gordon H Williams |
Related Documents
:
|
7977727 - Effect of central amiloride infusion on mineralocorticoid hypertension. 15030297 - The role of renin-angiotensin-aldosterone system inhibition in chronic kidney disease. 8138327 - Serotonergic mechanisms in hypertension. 15277317 - Effect of aldosterone antagonism on myocardial dysfunction in hypertensive patients wit... 7711467 - Atrial natriuretic peptide response to postural change and medication in familial dysau... 1343277 - The effect of manidipine on renal hemodynamics in essential hypertensive patients: resp... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural Date: 2006-10-02 |
Journal Detail:
|
Title: Hypertension Volume: 48 ISSN: 1524-4563 ISO Abbreviation: Hypertension Publication Date: 2006 Nov |
Date Detail:
|
Created Date: 2006-10-20 Completed Date: 2006-12-11 Revised Date: 2008-11-21 |
Medline Journal Info:
|
Nlm Unique ID: 7906255 Medline TA: Hypertension Country: United States |
Other Details:
|
Languages: eng Pagination: 892-900 Citation Subset: IM |
Affiliation:
|
Brigham and Women's Hospital, Division of Endocrinology, Diabetes, and Hypertension, 221 Longwood Ave, Boston, MA 02115, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adolescent Adult Aged Animals Female Genetic Variation Humans Hypertension / chemically induced, genetics*, metabolism Middle Aged Phenotype Polymorphism, Genetic Rats Rats, Wistar Receptors, Adrenergic, beta-2 / genetics*, physiology Sodium Chloride, Dietary* |
| Grant Support | |
ID/Acronym/Agency:
|
DK63214/DK/NIDDK NIH HHS; HL069208/HL/NHLBI NIH HHS; HL47651/HL/NHLBI NIH HHS; HL59424/HL/NHLBI NIH HHS; M01RR00064/RR/NCRR NIH HHS; M01RR00095/RR/NCRR NIH HHS; M01RR02635/RR/NCRR NIH HHS; P50HL055000/HL/NHLBI NIH HHS; T32HL007609/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Receptors, Adrenergic, beta-2; 0/Sodium Chloride, Dietary |
| Comments/Corrections | |
Comment In:
|
Hypertension. 2006 Nov;48(5):820-1
[PMID:
17015779
]
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Autonomic cardiovascular responses to heme oxygenase inhibition in conscious rats.
Next Document: Implication of chromosome 18 in hypertension by sibling pair and association analyses: putative invo...