Arginine vasopressin (AVP) is elevated in patients with heart failure, and the increase in the AVP concentration in plasma is positively correlated with disease severity and mortality. Metoprolol (Met) is a beta blocker that is widely used in the clinic to treat pathological cardiac hypertrophy and to improve heart function. However, the specific mechanism by which Met alleviates AVP-induced pathological cardiac hypertrophy is still unknown. Our current study aimed to evaluate the inhibitory effects of Met on AVP-induced cardiomyocyte hypertrophy and the underlying mechanisms. AVP alone or AVP plus Met was added to the wild type or AKT1-overexpressing rat cardiac H9C2 cell line. The cell surface areas and ANP/BNP/β-MHC expressions were used to evaluate the levels of hypertrophy. Western bolting was used to analyze AKT1/P-AKT1, AKT2/P-AKT2, total AKT, SERCA2, and Phospholamban (PLN) expression. Fluo3-AM was used to measure the intracellular Ca2+ stores. In the current study, we found that AKT1 but not AKT2 mediated the pathogenesis of AVP-induced cardiomyocyte hypertrophy. Sustained stimulation (48 h) with AVP led to hypertrophy in the H9C2 rat cardiomyocytes, resulting in the downregulation of AKT1 (0.48 fold compared to control) and SERCA2 (0.62 fold), the upregulation of PLN (1.32 fold), and the increase in the cytoplasmic calcium concentration (1.52 fold). In addition, AKT1 overexpression increased the expression of SERCA2 (1.34 fold) and decreased the expression of PLN (0.48 fold) in the H9C2 cells. Moreover, we found that Met could attenuate the AVP-induced changes in AKT1, SERCA2 and PLN expression and decreased the cytoplasmic calcium concentration in the H9C2 cells. Our results demonstrated that the AKT1–SERCA2 cascade served as an important regulatory pathway in AVP-induced pathological cardiac hypertrophy.

中文翻译：

---

Metoprolol 通过上调 H9C2 细胞中的 AKT1-SERCA2 级联反应来减轻精氨酸加压素诱​​导的心肌细胞肥大。

精氨酸加压素 (AVP) 在心力衰竭患者中升高，血浆中 AVP 浓度的升高与疾病严重程度和死亡率呈正相关。美托洛尔（Met）是一种β受体阻滞剂，临床上广泛用于治疗病理性心脏肥大和改善心脏功能。然而，Met 缓解 AVP 诱导的病理性心脏肥大的具体机制仍不清楚。我们目前的研究旨在评估 Met 对 AVP 诱导的心肌细胞肥大的抑制作用及其潜在机制。将单独的 AVP 或 AVP 加 Met 添加到野生型或过表达 AKT1 的大鼠心脏 H9C2 细胞系中。细胞表面积和 ANP/BNP/β-MHC 表达用于评估肥大水平。Western bolting 用于分析 AKT1/P-AKT1、AKT2/P-AKT2、总 AKT、SERCA2 和 Phospholamban (PLN) 表达。Fluo3-AM 用于测量细胞内 Ca2+ 储存。在目前的研究中，我们发现AKT1而非AKT2介导了AVP诱导的心肌细胞肥大的发病机制。AVP 持续刺激（48 小时）导致 H9C2 大鼠心肌细胞肥大，导致 AKT1（与对照相比为 0.48 倍）和 SERCA2（0.62 倍）下调，PLN 上调（1.32 倍），以及细胞质钙浓度（1.52 倍）。此外，AKT1 过表达增加了 H9C2 细胞中 SERCA2 的表达（1.34 倍）并降低了 PLN 的表达（0.48 倍）。此外，我们发现 Met 可以减弱 AVP 诱导的 AKT1、SERCA2 和 PLN 表达的变化，并降低 H9C2 细胞中的细胞质钙浓度。