Anzai T, Lai N C, Gao M, Hammond H K
Veterans Affairs Medical Center-San Diego and Department of Medicine, University of California San Diego, La Jolla, California 92161, USA.
Am J Physiol. 1998 Oct;275(4):H1267-73. doi: 10.1152/ajpheart.1998.275.4.H1267.
We have previously shown that left ventricular (LV) pacing-induced heart failure is associated with preserved wall thickening in the interventricular septum (IVS) compared with the posterolateral wall (PLW). The current study focuses on the relationship between regional myocardial function and altered beta-adrenergic receptor (beta-AR) signaling. We studied 15 pigs: 6 controls and 9 paced from the left ventricle (225 beats/min, 26 +/- 3 days). Heart failure was documented by decreased LV fractional shortening (P < 0.0001) and increased left atrial pressure (P < 0.0001). In heart failure, despite marked differences in basal regional function (percent wall thickening: IVS, 33 +/- 10% vs. PLW, 13 +/- 7%; P = 0.0003), there were no differences between the two regions in beta-AR responsiveness, measured by regional wall thickening in response to dobutamine infusion and any measurement of adrenergic signaling. Adenylyl cyclase activity, beta-AR number, and beta-AR/Gs coupling were markedly reduced in failing LV without regional differences. In animals with heart failure, LV G protein receptor kinase (GRK) isoform 2 content was unchanged and GRK5, the other major GRK isoform, was increased more than threefold (IVS, 0.51 +/- 0.20 vs. 0. 12 +/- 0.12 arbitrary densitometric units, P = 0.01; PLW, 0.47 +/- 0. 15 vs. 0.13 +/- 0.09 arbitrary densitometric units, P = 0.03), but again, there were no regional differences. These data indicate that systemic rather than regional factors govern LV adrenergic signaling and that regional adrenergic signaling abnormalities poorly predict wall thickening in the same regions.
我们之前已经表明，与后外侧壁（PLW）相比，左心室（LV）起搏诱导的心力衰竭与室间隔（IVS）壁增厚保留有关。当前的研究聚焦于局部心肌功能与β-肾上腺素能受体（β-AR）信号改变之间的关系。我们研究了15头猪：6头为对照，9头从左心室起搏（225次/分钟，26±3天）。通过左心室缩短分数降低（P<0.0001）和左心房压力升高（P<0.0001）记录心力衰竭。在心力衰竭中，尽管基础局部功能存在显著差异（壁增厚百分比：IVS为33±10%，PLW为13±7%；P = 0.0003），但通过多巴酚丁胺输注后的局部壁增厚以及任何肾上腺素能信号测量，两个区域在β-AR反应性方面没有差异。在衰竭的左心室中，腺苷酸环化酶活性、β-AR数量和β-AR/Gs偶联显著降低，且无区域差异。在心力衰竭的动物中，左心室G蛋白受体激酶（GRK）亚型2含量未改变，另一种主要的GRK亚型GRK5增加了三倍多（IVS，0.51±0.20对0.12±0.12任意光密度单位，P = 0.01；PLW，0.47±0.15对0.13±0.09任意光密度单位，P = 0.03），但同样没有区域差异。这些数据表明，全身性而非局部性因素控制左心室肾上腺素能信号，并且局部肾上腺素能信号异常不能很好地预测同一区域的壁增厚情况。
