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Gly¹⁶ + Glu²⁷ ₂-adrenoceptor polymorphisms cause increased forearm blood flow responses to mental stress and handgrip in humans

¹Heart Institute (InCor), Medical School, ²Department of Endocrinology, and ³School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil

Submitted 17 May 2004 ; accepted in final form 15 October 2004

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 ₂-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 ₂-adrenoceptors have augmented muscle vasodilatory responsiveness to mental stress and exercise.

exercise;; muscle vasodilatation

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