Snyder Eric M, Beck Kenneth C, Turner Stephen T, Hoffman Eric A, Joyner Michael J, Johnson Bruce D
Department of Internal Medicine, Mayo Clinic College of Medicine, 200 1st St., SW, Rochester, MN 55905, USA.
J Appl Physiol (1985). 2007 Jun;102(6):2172-8. doi: 10.1152/japplphysiol.01300.2006. Epub 2007 Mar 8.
The beta2-adrenergic receptors (beta2AR) play an important role in lung fluid regulation. Previous research has suggested that subjects homozygous for arginine at amino acid 16 of the beta2AR (Arg16) may have attenuated receptor function relative to subjects homozygous for glycine at the same amino acid (Gly16). We sought to determine if the Arg16Gly polymorphism of the beta2AR influenced lung fluid balance in response to rapid saline infusion. We hypothesized that subjects homozygous for Arg at amino acid 16 (n=14) would have greater lung fluid accumulation compared with those homozygous for Gly (n=15) following a rapid intravenous infusion of isotonic saline (30 ml/kg over 17 min). Changes in lung fluid were determined using measures of lung density and tissue volume (computerized tomography imaging) and measures of pulmonary capillary blood volume (Vc) and alveolar-capillary conductance (DM, determined from the simultaneous assessment of the diffusing capacities of the lungs for carbon monoxide and nitric oxide). The saline infusion resulted in elevated catecholamines in both genotype groups (Arg16 283+/-117% vs. Gly16 252+/-118%, P>0.05). The Arg16 group had a larger decrease in DM and increase in lung tissue volume and lung water after saline infusion relative to the Gly16 group (DM -13+/-14 vs. 0+/-26%, P<0.05; lung tissue volume 13+/-11 vs. 3+/-11% and lung water +90+/-66 vs. +48+/-144 ml, P=0.10, P<0.05, for Arg vs. Gly16, respectively, means+/-SD). These data suggest that subjects homozygous for Arg at amino acid 16 of the beta2AR have a greater susceptibility for lung fluid accumulation relative to subjects homozygous for Gly at this position.
β2 - 肾上腺素能受体（β2AR）在肺液调节中起重要作用。先前的研究表明，β2AR第16位氨基酸为精氨酸的纯合子受试者（Arg16）相对于同一氨基酸为甘氨酸的纯合子受试者（Gly16），其受体功能可能减弱。我们试图确定β2AR的Arg16Gly多态性是否会影响快速输注生理盐水后肺液平衡。我们假设，在快速静脉输注等渗盐水（17分钟内输注30 ml/kg）后，第16位氨基酸为Arg的纯合子受试者（n = 14）与第16位氨基酸为Gly的纯合子受试者（n = 15）相比，肺液积聚更多。使用肺密度和组织体积测量值（计算机断层扫描成像）以及肺毛细血管血容量（Vc）和肺泡 - 毛细血管传导率（DM，通过同时评估肺对一氧化碳和一氧化氮的弥散能力来确定）来测定肺液变化。生理盐水输注导致两个基因型组的儿茶酚胺水平升高（Arg16组为283±117%，Gly16组为252±118%，P>0.05）。相对于Gly16组，Arg16组在生理盐水输注后DM下降幅度更大，肺组织体积和肺水增加幅度更大（DM：-13±14%对0±26%，P<0.05；肺组织体积：13±11%对3±11%；肺水：+90±66对+48±144 ml，Arg组与Gly16组相比，P分别为0.10和P<0.05，均值±标准差）。这些数据表明，β2AR第16位氨基酸为Arg的纯合子受试者相对于该位置为Gly的纯合子受试者，肺液积聚的易感性更高。
