Snyder Eric M, Beck Kenneth C, Dietz Niki M, Eisenach John H, Joyner Michael J, Turner Stephen T, Johnson Bruce D
Department of Internal Medicine, Division of Cardiovascular Diseases, Mayo Clinic and Foundation, 200 1st Street, SW, Rochester, MN 55905, USA.
J Physiol. 2006 Feb 15;571(Pt 1):121-30. doi: 10.1113/jphysiol.2005.098558. Epub 2005 Dec 8.
In humans, subjects homozygous for arginine (ArgArg) at codon 16 of the beta2-adrenergic receptor (beta2AR) have been shown to have greater agonist-mediated desensitization than subjects homozygous for glycine (GlyGly). We sought to determine if this substitution differentially influenced cardiovascular function during short duration (9 min) low and high intensity exercise (40 and 75% of peak work). Healthy Caucasian ArgArg (n = 16), GlyGly (n = 31) and ArgGly (n = 17) subjects matched for age, sex and peak oxygen uptake were studied. There were no differences in adrenaline (ADR) at rest or with heavy exercise, but the ArgArg group had lower ADR with light exercise (P = 0.04). Resting heart rate (HR) was higher in ArgArg (P < 0.01), while cardiac output (Q), stroke volume (SV), and mean arterial pressure (MAP) were lower than the other groups (HR = 86+/-2, 78+/-2, 80+/-1 beats min(-1); Q = 5.7+/-0.81, 6.1+/-0.18, 6.7+/-0.22 l min(-1); SV = 68+/-3, 82+/-3, 89+/-4 ml beat(-1); MAP = 92+/-1, 103+/-2, 98+/-1 mmHg-- for ArgArg, ArgGly and GlyGly, respectively, means +/-s.e.m., P < 0.01), however, no differences were observed in systemic vascular resistance (SVR). With low intensity exercise and high intensity exercise the ArgArg group continued to have a lower , SV and MAP compared to the other groups (P < 0.05), with no differences observed in SVR. During recovery, the ArgArg subjects continued to have a lower MAP but there were no differences in HR, , or SVR. These data suggest that subjects homozygous for Arg at codon 16 of the beta2AR have reduced and MAP at rest that persist during exercise with no evidence for differential changes over the course of exercise despite large changes in catecholamines. This may suggest possible genotype-related differences in baseline receptor function or density which causes phenotypic differences at rest that are sustained during short-term exercise.
在人类中，已表明β2肾上腺素能受体（β2AR）第16密码子为精氨酸纯合子（ArgArg）的受试者比甘氨酸纯合子（GlyGly）的受试者具有更强的激动剂介导的脱敏作用。我们试图确定这种替换在短时间（9分钟）低强度和高强度运动（分别为峰值运动的40%和75%）期间是否对心血管功能有不同影响。对年龄、性别和峰值摄氧量相匹配的健康白种人ArgArg（n = 16）、GlyGly（n = 31）和ArgGly（n = 17）受试者进行了研究。静息或剧烈运动时肾上腺素（ADR）无差异，但ArgArg组轻度运动时ADR较低（P = 0.04）。ArgArg组静息心率（HR）较高（P < 0.01），而心输出量（Q）、每搏输出量（SV）和平均动脉压（MAP）低于其他组（HR = 86±2、78±2、80±1次/分钟；Q = 5.7±0.81、6.1±0.18、6.7±0.22升/分钟；SV = 68±3、82±3、89±4毫升/次；MAP = 92±1、103±2、98±1 mmHg——分别为ArgArg、ArgGly和GlyGly组，均值±标准误，P < 0.01），然而，全身血管阻力（SVR）无差异。与其他组相比，低强度运动和高强度运动时ArgArg组的Q、SV和MAP持续较低（P < 0.05），SVR无差异。恢复期间，ArgArg受试者的MAP持续较低，但HR、Q或SVR无差异。这些数据表明，β2AR第16密码子为Arg纯合子的受试者静息时的Q和MAP降低，运动期间持续存在，尽管儿茶酚胺有很大变化，但运动过程中无差异变化的证据。这可能表明基线受体功能或密度存在与基因型相关的差异，导致静息时的表型差异在短期运动中持续存在。
