β 2 ‐Adrenoceptor gene variation and systemic vasodilatation during ganglionic blockade

Regional infusions of β 2 ‐adrenoceptor (ADRB2) agonist have generally shown that individuals homozygous for Gly16 produces greater vasodilatation than those homozygous for Arg16. Systemic infusions have shown an opposite effect on systemic vascular resistance (SVR), possibly confounded by baroreflexes or interactions between single nucleotide polymorphism (SNP) positions 16 and 27. We tested the hypothesis that ADRB2 gene variation would influence the SVR response to ADRB2 agonist terbutaline (Terb) during ganglionic blockade. Forty healthy young adults were recruited according to the double homozygous haplotypes: Arg16 + Gln27 ( n = 13), the rare Gly16 + Gln27 ( n = 6), and Gly16 + Glu27 ( n = 21). Arterial pressure was measured by brachial arterial catheter, and 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 −1 ), continuous phenylephrine was titrated to restore blood pressure to baseline. Terb was infused i.v. at 33 and 67 ng kg −1 min −1 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 (mean ± s.e.m. : 7.5 ± 0.4) vs. Arg16 (8.9 ± 0.7 units; P = 0.03). Lymphocyte ADRB2 binding conformation was similar but receptor density was greater in Gly16 vs. Arg16 ( P = 0.05). We conclude that during ganglionic blockade, the SVR response to systemic ADRB2 agonist is suggestive of augmented ADRB2 function in Gly16 + Glu27 homozygotes, with greater influence from Gly16, providing further evidence that ADRB2 gene variation influences vasodilatation. Adrenaline and noradrenaline stimulate vasodilatation by binding to the β 2 ‐adrenoceptor. This receptor shows genetic variation in humans. When infusions that activate the β 2 ‐adrenoceptor are administered in isolated limb vessels, individuals homozygous for glycine at position 16 (Gly16) or glutamate at position 27 (Glu27) of the receptor protein show greater vasodilatation than those from individuals homozygous for arginine at position 16 (Arg16) or glutamine at position 27 (Gln27). This study demonstrated that a similar result is found with systemic (total‐body) activation, so long as baroreflex control of the circulation is inhibited. This may reconcile previous discrepancies between regional and systemic infusion studies and, at a minimum