Rosuvastatin is one of the most used statins to lower plasma cholesterol levels. Although previous studies have reported remarkable cardiovascular effects of rosuvastatin (RSV), the mechanisms of these effects are largely unknown. In this study, we investigated the acute effects of RSV on L-type Ca²⁺ currents and contractile function of ventricular myocytes under basal conditions and during β-adrenergic stimulation. The effects of RSV were investigated in freshly isolated adult rat ventricular myocytes. L-type Ca⁺² currents and myocyte contractility were recorded using patch-clamp amplifier and sarcomere length detection system. All experimental recordings were performed at 36 ± 1 °C. L-type Ca⁺² currents were significantly reduced with the administration of 1 μM RSV (~ 24%) and this reduction in Ca²⁺ currents was observed at almost all potential ranges applied. Suppression of L-type Ca²⁺ current by RSV was prevented by adenylyl cyclase (AC) and protein kinase A (PKA) inhibitors SQ 22536 and KT5720, respectively. However, inhibition of Rho-associated kinases (ROCKs) by Y-27632 or nitric oxide synthase (NOS) by L-NAME failed to circumvent the inhibitory effect of RSV. Finally, we examined the effect of RSV during β-adrenergic receptor stimulation by isoproterenol and observed that RSV significantly suppresses the β-adrenergic responses in both L-type Ca²⁺ currents and contraction parameters. In conclusion, RSV modulates the β-adrenergic signaling cascade and thereby mimics the impact of β-adrenergic receptor blockers in adult ventricular myocytes through modulation of the AC-cAMP-PKA pathway.

瑞舒伐他汀是最常用的降低血浆胆固醇水平的他汀类药物之一。尽管之前的研究报道了瑞舒伐他汀 (RSV) 对心血管的显着影响，但这些影响的机制在很大程度上尚不清楚。在这项研究中，我们研究了RSV 在基础条件下和β-肾上腺素能刺激过程中对L 型Ca ²⁺电流和心室肌细胞收缩功能的急性影响。在新鲜分离的成年大鼠心室肌细胞中研究了 RSV 的影响。使用膜片钳放大器和肌节长度检测系统记录L型Ca ⁺²电流和心肌细胞收缩力。所有实验记录均在 36 ± 1 °C 下进行。施用 1 μM RSV (~ 24%) 后，L 型 Ca ⁺²电流显着降低，并且在几乎所有施加的电位范围内都观察到 Ca ²⁺电流的这种降低。 RSV 对 L 型 Ca ²⁺电流的抑制可分别被腺苷酸环化酶 (AC) 和蛋白激酶 A (PKA) 抑制剂 SQ 22536 和 KT5720 阻止。然而，Y-27632 抑制 Rho 相关激酶 (ROCK) 或 L-NAME 抑制一氧化氮合酶 (NOS) 未能规避 RSV 的抑制作用。最后，我们检查了RSV在异丙肾上腺素刺激β-肾上腺素受体期间的作用，并观察到RSV显着抑制L-型Ca ²⁺电流和收缩参数中的β-肾上腺素能反应。总之，RSV 调节 β-肾上腺素能信号级联，从而通过调节 AC-cAMP-PKA 途径模拟 β-肾上腺素能受体阻滞剂对成人心室肌细胞的影响。