Interactions between beta-2 adrenoceptor gene variation, cardiovascular control and dietary sodium in healthy young adults

John H. Eisenach, Darrell R. Schroeder, Emily S. Pavey, Alan R. Penheiter, Jean N. Knutson, Stephen T Turner, Michael Joseph Joyner

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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). Using a randomized cross-over design, subjects were studied following 5 days of controlled low, normal and high sodium with 1 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 the Gly16+Glu27 haplotype having the greatest density (low, normal, high sodium: 12.9 ± 0.9, 13.5 ± 0.9 and 13.6 ± 0.8 fmol mg-1 protein, respectively) and Arg16+Gln27 having the least (9.3 ± 0.6, 10.1 ± 0.5 and 10.3 ± 0.6 fmol mg-1 protein, respectively), 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.

Original languageEnglish (US)
Pages (from-to)5221-5233
Number of pages13
JournalJournal of Physiology
Volume592
Issue number23
DOIs
StatePublished - Dec 1 2014

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Dietary Sodium
Adrenergic Receptors
Haplotypes
Young Adult
Sodium
Genes
Forearm
Plethysmography
Hemodynamics
Vasodilator Agents
Vasodilation
Diet
Proteins
Menstrual Cycle
Isoproterenol
Cardiac Output
Cross-Over Studies
Fingers
Electrocardiography
Arm

ASJC Scopus subject areas

  • Physiology

Cite this

Interactions between beta-2 adrenoceptor gene variation, cardiovascular control and dietary sodium in healthy young adults. / Eisenach, John H.; Schroeder, Darrell R.; Pavey, Emily S.; Penheiter, Alan R.; Knutson, Jean N.; Turner, Stephen T; Joyner, Michael Joseph.

In: Journal of Physiology, Vol. 592, No. 23, 01.12.2014, p. 5221-5233.

Research output: Contribution to journalArticle

Eisenach, John H. ; Schroeder, Darrell R. ; Pavey, Emily S. ; Penheiter, Alan R. ; Knutson, Jean N. ; Turner, Stephen T ; Joyner, Michael Joseph. / Interactions between beta-2 adrenoceptor gene variation, cardiovascular control and dietary sodium in healthy young adults. In: Journal of Physiology. 2014 ; Vol. 592, No. 23. pp. 5221-5233.
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