The dynamic nature of the microtubule network is dependent in part by post-translational modifications (PTMs) — particularly through acetylation, which stabilizes the microtubule network. Whether PTMs of the microtubule network in vascular smooth muscle cells (VSMCs) contribute to the pathophysiology of hypertension is unknown. The aim of this study was to determine the acetylated state of the microtubule network in the mesenteric arteries of spontaneously hypertensive rats (SHR). Experiments were performed on male normotensive rats and SHR mesenteric arteries. Western blotting and mass spectrometry determined changes in tubulin acetylation. Wire myography was used to investigate the effect of tubacin on isoprenaline-mediated vasorelaxations. Isolated cells from normotensive rats were used for scanning ion conductance microscopy (SICM). Mass spectrometry and Western blotting showed that tubulin acetylation is increased in the mesenteric arteries of the SHR compared with normotensive rats. Tubacin enhanced the β-adrenoceptor-mediated vasodilatation by isoprenaline when the endothelium was intact, but attenuated relaxations when the endothelium was denuded or nitric oxide production was inhibited. By pre-treating vessels with colchicine to disrupt the microtubule network, we were able to confirm that the effects of tubacin were microtubule-dependent. Using SICM, we examined the cell surface Young's modulus of VSMCs, but found no difference in control, tubacin-treated, or taxol-treated cells. Acetylation of tubulin at Lys40 is elevated in mesenteric arteries from the SHR. Furthermore, this study shows that tubacin has an endothelial-dependent bimodal effect on isoprenaline-mediated vasorelaxation.

中文翻译：

---

高血压大鼠肠系膜动脉平滑肌细胞微管乙酰化增加

微管网络的动态性质部分取决于翻译后修饰（PTM）——特别是通过乙酰化，它可以稳定微管网络。血管平滑肌细胞 (VSMC) 中微管网络的 PTM 是否有助于高血压的病理生理学尚不清楚。本研究的目的是确定自发性高血压大鼠 (SHR) 肠系膜动脉中微管网络的乙酰化状态。实验在雄性血压正常的大鼠和 SHR 肠系膜动脉上进行。蛋白质印迹和质谱测定微管蛋白乙酰化的变化。钢丝肌动描记法用于研究图巴星对异丙肾上腺素介导的血管舒张的影响。使用来自正常血压大鼠的分离细胞进行扫描离子电导显微镜（SICM）。质谱和蛋白质印迹显示，与血压正常的大鼠相比，SHR 肠系膜动脉中的微管蛋白乙酰化增加。当内皮完整时，Tubacin 增强异丙肾上腺素介导的 β-肾上腺素受体介导的血管舒张作用，但在内皮剥脱或一氧化氮产生受到抑制时减弱舒张作用。通过用秋水仙碱预处理血管以破坏微管网络，我们能够证实tubacin的作用是微管依赖性的。使用 SICM，我们检查了 VSMC 的细胞表面杨氏模量，但发现对照、经tubacin 处理或经紫杉醇处理的细胞没有差异。来自 SHR 的肠系膜动脉中微管蛋白 Lys40 的乙酰化升高。此外，这项研究表明，tubacin 对异丙肾上腺素介导的血管舒张具有内皮依赖性双模式作用。