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.

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Hereditary 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]-resistant rickets (HVDRR) is a rare autosomal recessive disorder resulting in target organ resistance to the active form of vitamin D [1,25-(OH)2D3]. Point mutations in the vitamin D receptor (VDR) gene have been identified in HVDRR. We investigated the molecular basis of HVDRR in a Brazilian family with two affected siblings. The propositus is a 12-yr-old boy born to first cousin parents who exhibited the classical pattern of the HVDRR, including early-onset rickets, total alopecia, convulsions, hypocalcemia, secondary hyperparathyroidism, and elevated 1,25-(OH)2D3 serum levels. His younger sister also developed clinical and biochemical features of HVDRR at 1 month of age and died at 4 yr of age. Genomic DNA was isolated from peripheral blood of the boy and from dried umbilical cord tissue of his affected sister. We amplified exons 2 and 3 of the VDR gene, which encode the zinc finger DNA-binding domain by PCR. Direct sequencing of the PCR products revealed a homozygous substitution of cytosine for thymine at nucleotide position 88 in exon 2 of the VDR gene in both affected siblings. This point mutation determined the substitution of a stop codon (TGA) for arginine (CGA) at amino acid position 30 at the first zinc finger of the DNA-binding domain of the VDR. This substitution generated a truncated receptor missing 397 residues. The parents and a normal sister were heterozygous for this mutation. In conclusion, we describe a novel nonsense mutation in the first zinc finger of the VDR that generated a severely truncated form of this receptor.

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Objective: To investigate the association of short form (Glu 9 /Glu 9 ) of the 12Glu9 deletion polymorphism of the a 2B -adrenergic receptor (a 2B -AR) gene polymorphism with the cardiac autonomic responsiveness during sustained isometric handgrip exercise. Design: Cross-sectional clinical study. Subjects: In all, 97 normotensive obese women (body mass index (BMI) ¼ 33.2 kg/m 2 ). Of these, 78 (80.41%) were genotyped as Glu 12 /Glu 12 , 13 (13.40%) as Glu 12 /Glu 9 and six (6.19%) as Glu 9 /Glu 9 form. Measurements: The sympathovagal balance was assessed by means of power spectral analysis of heart rate variability at rest and during sustained isometric handgrip exercise at 30% of maximal voluntary handgrip contraction for 3 min. Two spectral components were analysed: low-frequency component reflecting sympathetic efferent activity and high-frequency power (HFnu) reflecting parasympathetic modulation. In addition, a normalized low-frequency power (LFnu) and HFnu were analysed. Genotypes were determined by polymerase chain reaction followed by agarose gel electrophoresis. Results: There were no differences in baseline measurements among groups. The absolute level of LFnu throughout handgrip exercise was significantly lower in Glu 9 /Glu 9 subjects compared with other genotypes, while the decline of absolute HFnu was significantly smaller compared with Glu 12 /Glu 12 genotype. Conclusion: These findings suggest that 12Glu9 deletion polymorphism of the a 2B -AR gene (Glu 9 /Glu 9 genotype) might result in reduced autonomic responsiveness by altering cardiac sympathetic and vagal function during sustained handgrip exercise in normotensive obese women.

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This study examined forearm vasodilatation during mental challenge and exercise in 72 obese children (OC; age = 10 ± 0.1 years) homozygous with polymorphism in the allele 27 of the β2-adrenoceptors: Gln27 (n = 61) and Glu27 (n = 11). Forearm blood flow was recorded during 3 min of each using the Stroop color-word test (MS) and handgrip isometric exercise. Baseline hemodynamic and vascular measurements were similar. During the MS, peak forearm vascular conductance was significantly greater in group Glu27 (Δ = 0.35 ± 0.4 vs. 0.12 ± 0.1 units, respectively, p = .042). Similar results were found during exercise (Δ = 0.64 ± 0.1 vs. 0.13 ± 0.1 units, respectively, p = .035). Glu27 OC increased muscle vasodilatory responsiveness upon the MS and exercise.

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