Vascular aging influences hemodynamics, elevating risks for vascular diseases and dementia. We recently demonstrated that knockout (KO) of Dusp5 enhances cerebral and renal hemodynamics and cognitive function. This improvement correlates with elevated pPKC and pERK1/2 levels in the brain and kidneys. Additionally, we observed that Dusp5 KO modulates the passive mechanical properties of cerebral and renal arterioles, associated with increased myogenic tone at low pressure, enhanced distensibility, greater compliance, and reduced stiffness. The present study evaluates the structural and mechanical properties of the middle cerebral artery (MCA) in Dusp5 KO rats. We found that vascular smooth muscle cell layers and the collagen content in the MCA wall are comparable between Dusp5 KO and control rats. The internal elastic lamina in the MCA of Dusp5 KO rats exhibits increased thickness, higher autofluorescence intensity, smaller fenestrae areas, and fewer fenestrations. Despite an enhanced myogenic response and tone of the MCA in Dusp5 KO rats, other passive mechanical properties, such as wall thickness, cross-sectional area, wall-to-lumen ratio, distensibility, incremental elasticity, circumferential wall stress, and elastic modulus, do not significantly differ between strains. These findings suggest that while Dusp5 KO has a limited impact on altering the structural and mechanical properties of MCA, its primary role in ameliorating hemodynamics and cognitive functions is likely attributable to its enzymatic activity on cerebral arterioles. Further research is needed to elucidate the specific enzymatic mechanisms and explore potential clinical applications in the context of vascular aging.

血管老化影响血流动力学，增加血管疾病和痴呆的风险。我们最近证明Dusp5的敲除 (KO)可增强脑和肾的血流动力学和认知功能。这种改善与大脑和肾脏中 pPKC 和 pERK1/2 水平的升高相关。此外，我们观察到Dusp5 KO 调节脑和肾小动脉的被动机械特性，与低压下肌源性张力增加、扩张性增强、顺应性提高和硬度降低相关。本研究评估了Dusp5 KO 大鼠大脑中动脉 (MCA) 的结构和机械特性。我们发现Dusp5 KO 大鼠和对照大鼠之间的血管平滑肌细胞层和 MCA 壁中的胶原蛋白含量相当。Dusp5 KO大鼠大脑中动脉的内弹性层厚度增加，自发荧光强度更高，窗孔面积更小，开窗数量更少。尽管Dusp5 KO 大鼠的 MCA 肌源性反应和张力增强，但其他被动机械特性，如壁厚度、横截面积、壁与腔比率、扩张性、增量弹性、周壁应力和弹性模量，菌株之间没有显着差异。这些发现表明，虽然Dusp5 KO 对改变 MCA 的结构和机械特性影响有限，但其改善血流动力学和认知功能的主要作用可能归因于其对脑小动脉的酶活性。需要进一步的研究来阐明特定的酶促机制并探索在血管老化背景下的潜在临床应用。