Leineweber Kirsten, Bruck Heike, Temme Thomas, Heusch Gerd, Philipp Thomas, Brodde Otto-Erich
Department of Nephrology, University of Essen Medical School, Germany.
Pharmacogenet Genomics. 2006 Jan;16(1):9-13. doi: 10.1097/01.fpc.0000184956.16077.93.
In vitro, Arg389Gly beta1-adrenoceptor (AR) polymorphism exhibits decreased beta-AR signalling. In vivo, beta1-AR-mediated cardiac effects of exercise showed no genotype-dependent differences in Arg389 vs. Gly389 beta1-AR subjects. We studied in 16 male subjects homozygous Arg389 or Gly389 beta1-AR, whether blockade of parasympathetic activity might unmask genotype-dependence of exercise effects. Subjects were infused with atropine (10 microg/kg i.v. loading dose followed by continuous i.v. infusion of 0.15 microg/kg/min throughout exercise-time); 20 min after start of atropine bicycle-exercise in supine position (25, 50, 75 and 100 W for 5 min each) was performed and heart rate, contractility, blood pressure, plasma noradrenaline and plasma-renin activity were assessed. Exercise-evoked increases in all but one parameters were not different between Arg389 and Gly389 beta1-AR subjects; only plasma noradrenaline increased slightly more in Gly389 vs. Arg389 beta1-AR subjects.
It appears to be unlikely that lack of Arg389Gly beta1-AR genotype-dependence of exercise-effects can be explained by influences of parasympathetic activity.
在体外，精氨酸389甘氨酸β1-肾上腺素能受体（AR）多态性表现出β-AR信号传导降低。在体内，运动的β1-AR介导的心脏效应在精氨酸389与甘氨酸389β1-AR受试者中未显示出基因型依赖性差异。我们在16名纯合精氨酸389或甘氨酸389β1-AR的男性受试者中研究了副交感神经活动的阻断是否可能揭示运动效应的基因型依赖性。给受试者输注阿托品（静脉注射负荷剂量10微克/千克，随后在整个运动时间内以0.15微克/千克/分钟的速度持续静脉输注）；在开始输注阿托品20分钟后，受试者仰卧位进行自行车运动（25、50、75和100瓦，各持续5分钟），并评估心率、收缩力、血压、血浆去甲肾上腺素和血浆肾素活性。除一项参数外，精氨酸389和甘氨酸389β1-AR受试者运动诱发的其他参数增加无差异；仅甘氨酸389β1-AR受试者的血浆去甲肾上腺素增加略多于精氨酸389β1-AR受试者。
运动效应缺乏精氨酸389甘氨酸β1-AR基因型依赖性似乎不太可能由副交感神经活动的影响来解释。
