Characterization of cardiac myocyte and tissue β-adrenergic signal transduction in rats with heart failure
Characterization of cardiac myocyte and tissue β-adrenergic signal transduction in rats with heart failure
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DOI：
10.1016/s0008-6363(01)00203-6
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发表时间：
2001-04-01
影响因子：
10.8
通讯作者：
Takeo, S
中科院分区：
文献类型：
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作者：
Yoshida, H;Tanonaka, K;Takeo, S
目的：慢性心力衰竭（CHF）大鼠β-肾上腺素能信号转导改变的细胞基础仍不清楚。本研究的目的是检查 CHF 大鼠离体心室心肌细胞中的信号转导系统。我们重点关注刺激性 (Gs) 和抑制性 G 蛋白 (Gi) 水平的变化。方法：通过冠状动脉结扎（CAL）在雄性 Wistar 大鼠中诱导 CHF。 CAL后8周测量血流动力学和生化参数。通过同时测量细胞缩短和 fura-2 荧光强度来表征从 CHF 大鼠中分离的心肌细胞通过 β-肾上腺素能受体信号传导引起的收缩功能和 Ca2+ 瞬变的变化。结果：冠状动脉结扎大鼠术后8周出现CHF症状，如收缩功能下降、左心室容积增加、心室硬度降低以及约40%的左心室梗死形成。 CHF大鼠心肌细胞的收缩功能和Ca2+动态在基础条件下保持正常。仅心肌细胞长度增加。 CHF大鼠心肌细胞的峰值缩短、fura-2荧光比值幅度和cAMP含量对β-肾上腺素能受体刺激的反应降低，而直接刺激腺苷酸环化酶并不影响这些变量的反应。心肌细胞 Gs α 蛋白减少，而 Gi α 蛋白在这些细胞中未见变化。检测到疤痕区组织 Gs α 和 Gi α 蛋白增加。存活左心室中胶原蛋白和 G 蛋白的组织水平结果似乎取决于非肌细胞的存在。结论：结果表明，心肌细胞收缩功能受损不太可能解释左室整体收缩功能障碍，并且β-肾上腺素能受体的下调发生在心肌细胞本身中。心肌细胞和心肌组织之间 G 蛋白变化的差异表明非心肌细胞对心肌 G 蛋白水平有显着贡献。 (C) 2001 Elsevier Science B.V. 保留所有权利。
Objective: The cellular basis of alterations in beta -adrenergic signal transduction in rats with chronic heart failure (CHF) remains unclear. The aim of the present study was to examine this signal transduction system in isolated ventricular cardiomyocytes of rats with CHF. We focused on changes in the levels of stimulatory (Gs) and inhibitory G-proteins (Gi). Methods: CHF was induced in male Wistar rats by coronary artery ligation (CAL). Hemodynamic and biochemical parameters were measured 8 weeks after CAL. Alterations in contractile function and Ca2+ transients via beta -adrenergic receptor signaling of cardiomyocytes isolated from rats with CHF were characterized by simultaneous measurements of cell shortening and fura-2 fluorescence intensity. Results: Coronary artery-ligated rats showed symptoms of CHF, such as decreased contractile function, increased left ventricular volume, decreased chamber stiffness, and about 40% infarct formation of the left ventricle, by 8 weeks after surgery. The contractile function and Ca2+ dynamics of cardiomyocytes from the rats with CHF remained normal under basal conditions. Only cardiac cell length was increased. The responses of peak shortening, fura-2 fluorescence ratio amplitude, and cAMP content to beta -adrenoceptor stimulation were reduced in cardiomyocytes of the rats with CHF, whereas direct stimulation of adenylate cyclase did not affect the response of these variables. Cardiomyocyte Gs alpha protein was decreased, whereas no changes in Gi alpha proteins were seen in these cells. Increases in tissue Gs alpha and Gi alpha proteins in the scar zone were detected. The results on tissue levels of collagen and G-proteins in the viable left ventricle appeared to depend on the presence of nonmyocytes. Conclusions: The results suggest that impaired contractile function of cardiomyocytes is unlikely to account for global LV contractile dysfunction, and that down-regulation of beta -adrenoceptors occurs in cardiomyocytes per se. The difference in changes of G-protein between the cardiomyocyte and myocardial tissue suggests an appreciable contribution of nonmyocytes to myocardial G-protein levels. (C) 2001 Elsevier Science B.V. All rights reserved.