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Interactions between Beta-2 Adrenoceptor Gene Variation, Cardiovascular Control, and Dietary Sodium in Healthy Young Adults.
MedLine Citation:
PMID:  25260632     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Dietary sodium affects function of the beta-2 adrenoceptor (ADRB2). We tested the hypothesis that haplotype variation in the ADRB2 gene would influence the cardiovascular and regional vasodilator responses to sympathoexcitatory manoeuvres following low, normal, and high sodium diets, and ADRB2-mediated forearm vasodilation in the high sodium condition. Seventy-one healthy young adults were grouped by double homozygous haplotypes: Arg16+Gln27 (n = 31), the rare Gly16+Gln27 (n = 10), and Gly16+Glu27 (n = 30). By randomized cross-over design, subjects were studied following 5 days of controlled low, normal, and high sodium with one month or longer between diets (and low hormone phase of the menstrual cycle). All three visits utilized ECG and finger plethysmography for haemodynamic measures, and the high sodium visit included a brachial arterial catheter for forearm vasodilator responses to isoprenaline with plethysmography. Lymphocytes were sampled for ex vivo analysis of ADRB2 density and binding conformation. We found a main effect of haplotype on ADRB2 density (p = 0.03) with Gly16+Glu27 haplotype having the greatest density (low, normal, high sodium: 12.9±0.9, 13.5±0.9, 13.6±0.8 fmol/mg protein, resp.) and Arg16+Gln27 having the least (9.3±0.6, 10.1±0.5, 10.3±0.6, resp.), but there were no sodium or haplotype effects on receptor binding conformation. In the mental stress trial, there was a main effect of haplotype on cardiac output (p = 0.04), as Arg16+Gln27 had the lowest responses. Handgrip and forearm vasodilation yielded no haplotype differences, and no correlations were present for ADRB2 density and haemodynamics. Our findings support cell-based evidence that ADRB2 haplotype influences ADRB2 protein expression independent of dietary sodium, yet the haemodynamic consequences appear modest in healthy humans. This article is protected by copyright. All rights reserved.
Authors:
John H Eisenach; Darrell R Schroeder; Emily S Pavey; Alan R Penheiter; Jean N Knutson; Stephen T Turner; Michael J Joyner
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-9-25
Journal Detail:
Title:  The Journal of physiology     Volume:  -     ISSN:  1469-7793     ISO Abbreviation:  J. Physiol. (Lond.)     Publication Date:  2014 Sep 
Date Detail:
Created Date:  2014-9-27     Completed Date:  -     Revised Date:  2014-9-28    
Medline Journal Info:
Nlm Unique ID:  0266262     Medline TA:  J Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
This article is protected by copyright. All rights reserved.
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