β-2 adrenergic receptor variants affect resting blood pressure and agonist-induced vasodilation in young adult Caucasians

β-2 adrenergic receptor variants affect resting blood pressure and agonist-induced vasodilation in young adult Caucasians
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DOI:
10.1161/01.hyp.33.6.1425
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发表时间:
1999-06-01
期刊:
影响因子:
8.3
通讯作者:
Skrabal, F
Skrabal, F
中科院分区:
医学1区
文献类型:
--
作者:
Gratze, G;Fortin, J;Skrabal, F

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最近的证据表明,β-2肾上腺素能受体(β-2 AR)的前下调Gly 16等位基因与非洲加勒比人的原发性高血压有关。为了进一步研究甘氨酸(Gly)16和精氨酸(Arg)16 β-2 AR变体对血流动力学的影响,我们研究了血压正常的奥地利高加索人中激动剂介导的体内血管舒张,并分析了Gly 16/Arg 16多态性的结果。57名血压正常的男性,年龄20 ~ 32岁,体重指数18.7 ~ 29.9 kg/m2,进行Arg 16/Gly 16 β-2 AR等位基因的基因分型。所有15例Gly 16/Gly 16受试者、所有12例Arg 16/Arg/16受试者和30例杂合子受试者中的27例受试者在空腹过夜后仰卧位时接受血流动力学测量。观察者不知道受试者的基因型。受试者接受了选择性β-2 AR激动剂沙丁胺醇的分级输注(分别为0.07、0.14和0.21 μ g/kg/min),每次剂量超过8分钟。心搏量和血压分别通过心阻抗图和血压计连续测定。对每次输注的最后4分钟进行统计学评价。Gly 16/Gly 16受试者的基础平均血压高于Arg 16/Arg 16受试者(平均值± SD:81.6 ± 6.14 vs 75.2 ± 4.93 mmHg,P
Recent evidence suggests that the prodownregulatory Gly16 allele of the beta-2 adrenergic receptor (beta-2 AR) is associated with essential hypertension in African Caribbeans. To further investigate the effect of the glycine (Gly)16 and arginine (Arg)16 beta-2 AR variants on hemodynamics, we investigated the agonist-mediated in vivo vasodilation in normotensive Austrian Caucasians and analyzed the results with respect to the Gly16/Arg16 polymorphism. Fifty-seven normotensive men, 20 to 32 years of age with body mass index of 18.7 to 29.9 kg/m(2), were genotyped for the Arg16/Gly16 beta-2 AR alleles. All 15 Gly16/Gly16 subjects, all 12 Arg16/Arg/16 subjects, and 27 of 30 heterozygous subjects underwent hemodynamic measurements while supine after an overnight fast. The observers were unaware of the subjects' genotypes. The subjects received a graded infusion of the selective beta-2 AR agonist salbutamol (0.07, 0.14, and 0.21 mu g/kg per minute, respectively), each dose over 8 minutes. Stroke volume and blood pressure were determined continuously by means of impedance cardiography and oscillometry, respectively. The last 4 minutes of each infusion were evaluated statistically. Basal mean blood pressure was higher in the Gly16/Gly16 subjects compared with Arg16/Arg16 subjects (mean+/-SD: 81.6+/-6.14 versus 75.2+/-4.93 mmHg, P