Gly¹⁶ + Glu²⁷ β₂-adrenoceptor polymorphisms cause increased forearm blood flow responses to mental stress and handgrip in humans

Abstract

We hypothesized that the muscle vasodilatation during mental stress and exercise would vary among humans who are polymorphic at alleles 16 and 27 of the β2-adrenoceptors. From 216 preselected volunteers, we studied 64 healthy, middle-aged normotensive women selected to represent three genotypes: homozygous for the alleles Arg16 and Gln27 (Arg16/Gln27, n = 34), Gly16 and Gln27 (Gly16/Gln27, n = 20), and Gly16 and Glu27 (Gly16/Glu27, n = 10). Forearm blood flow (plethysmography) and muscle sympathetic nerve activity (microneurography) were recorded during 3-min Stroop color-word test and 3-min handgrip isometric exercise (30% maximal voluntary contraction). Baseline muscle sympathetic nerve activity, forearm vascular conductance, mean blood pressure, and heart rate were not different among groups. During mental stress, the peak forearm vascular conductance responses were greater in Gly16/Glu27 group than in Gly16/Gln27 and Arg16/Gln27 groups (1.79 ± 0.66 vs. 0.70 ± 0.11 and 0.58 ± 0.12 units, P = 0.03). Similar results were found during exercise (0.80 ± 0.25 vs. 0.28 ± 0.08 and 0.31 ± 0.08 units, P = 0.02). Further analysis in a subset of subjects showed that brachial intra-arterial propranolol infusion abolished the difference in vasodilatory response between Gly16/Glu27 ( n = 6) and Arg16/Gln27 ( n = 7) groups during mental stress (0.33 ± 0.20 vs. 0.46 ± 0.21 units, P = 0.50) and exercise (0.08 ± 0.06 vs. 0.03 ± 0.03 units, P = 0.21). Plasma epinephrine concentration in Arg16/Gln27 and Gly16/Glu27 groups was similar. In conclusion, women who are homozygous for Gly16/Glu27 of the β2-adrenoceptors have augmented muscle vasodilatory responsiveness to mental stress and exercise.

Glu298Asp eNOS gene polymorphism causes attenuation in nonexercising muscle vasodilatation

“…Joyner's group has elegantly demonstrated that endothelium-mediated NO production during physiological maneuvers is partially dependent on direct ␤ 2 -adrenoceptor stimulation (6). In addition, we have recently found augmented nonexercising muscle vasodilation responses to isometric handgrip exercise in women who are homozygous for Gly 16 /Glu 27 of the ␤ 2 -adrenoceptors (29). Thus, we cannot rule out the possibility that the ␤ 2 -adrenoceptor's polymorphism explains the difference among genotypes in a gene-gene manner interaction in the present study.…”

Neurohumoral activation in heart failure: the role of adrenergic receptors

“…This result suggests that Gln 27 influences the responsiveness of heart failure patients to β-blocker therapy. In addition, we have recently reported that humans with polymorphism of β 2 -adrenergic receptor at codons 16 and 27, namely women who are homozygous for Arg 16 /Glu 27 haplotype, have augmented muscle vasodilatory response to mental stress and exercise (Trombetta et al 2005). Whether this result will be reproducible in heart failure patients is not known.…”

α2B-Adrenergic receptor deletion polymorphism and cardiac autonomic nervous system responses to exercise in obese women

“…This cuff inflated every 30 s, as described previously. 18,19 Body composition determination. Fat body mass and lean body mass parameters were assessed by whole-body dual-energy X-ray absorption anthropometry with HOLOGIC QDR-2000 densitometer.…”