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β 2 ‐adrenergic receptor gene variation and systemic vasodilation during baroreflex inhibition
Author(s) -
Hesse Christiane,
Schroeder Darrel R.,
Nicholson Wayne T.,
Hart Emma C.,
Penheiter Alan R.,
Turner Stephen T.,
Joyner Michael J.,
Eisenach John H.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.791.3
Subject(s) - baroreflex , phenylephrine , medicine , vasodilation , endocrinology , agonist , terbutaline , blood pressure , receptor , chemistry , heart rate , asthma
β 2 ‐adrenergic receptor (ADRB2) gene polymorphisms influence vasodilation, but studies investigating regional or systemic responses conflict, possibly due to counter‐regulatory baroreflex action during systemic β 2 ‐agonist infusion. We tested the hypothesis that ADRB2 gene variation would influence the SVR response to ADRB2 agonist terbutaline (TERB) during baroreflex inhibition. 40 healthy young adults were recruited according to the double homozygous haplotypes: Arg16+Gln27 (n=13), Gly16+Gln27 (n=6), and Gly16+Glu27 (n=21). Arterial pressure was measured by brachial arterial catheter, cardiac output by acetylene breathing. Lymphocytes were sampled for ex vivo analysis of ADRB2 density and binding conformation. Following baroreflex ablation with trimethaphan (3–7 mg/min), phenylephrine was titrated to restore blood pressure to baseline. TERB was infused i.v. at 33 and 67 ng/kg/min for 15 min/dose. There was partial evidence to suggest a main effect of haplotype on the change in SVR ( P = 0.06). For SNP position 16, the highest dose of TERB produced lower SVR in Gly16 vs Arg16 ( P = 0.03). Lymphocyte ADRB2 binding conformation was similar but receptor density was greater in Gly16 vs Arg16 ( P = 0.05). During baroreflex inhibition, the SVR response to systemic ADRB2 agonist is suggestive of augmented ADRB2 function in Gly16+Glu27 homozygotes, with greater influence from Gly16. Supported from NIH and DFG.