Department of Human Physiology, 3265, University of Oregon, Eugene, OR, USA.
Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA.
J Cereb Blood Flow Metab. 2023 Feb;43(2):281-295. doi: 10.1177/0271678X221130124. Epub 2022 Oct 2.
Age-related increases in large artery stiffness are associated with cerebrovascular dysfunction and cognitive impairment. Pyridoxamine treatment prevents large artery stiffening with advancing age, but the effects of pyridoxamine treatment on the cerebral vasculature or cognition is unknown. The purpose of this study was to investigate the effects of pyridoxamine on blood pressure, large artery stiffness, cerebral artery function, and cognitive function in old mice. Old male C57BL/6 mice consumed either pyridoxamine (2 g/L) or vehicle control in drinking water for ∼7.5 months and were compared with young male C57BL/6 mice. From pre- to post-treatment, systolic blood pressure increased in old control mice, but was maintained in pyridoxamine treated mice. Large artery stiffness decreased in pyridoxamine-treated mice but was unaffected in control mice. Pyridoxamine-treated mice had greater cerebral artery endothelium-dependent dilation compared with old control mice, and not different from young mice. Old control mice had impaired cognitive function; however, pyridoxamine only partially preserved cognitive function in old mice. In summary, pyridoxamine treatment in old mice prevented age-related increases in blood pressure, reduced large artery stiffness, preserved cerebral artery endothelial function, and partially preserved cognitive function. Taken together, these results suggest that pyridoxamine treatment may limit vascular aging.
随着年龄的增长,大动脉僵硬与脑血管功能障碍和认知障碍有关。吡哆胺治疗可防止大动脉随年龄增长而变硬,但吡哆胺治疗对脑血管或认知的影响尚不清楚。本研究的目的是研究吡哆胺对老年小鼠血压、大动脉僵硬、脑动脉功能和认知功能的影响。雄性 C57BL/6 老年小鼠在饮用水中摄入吡哆胺(2g/L)或对照物约 7.5 个月,并与年轻雄性 C57BL/6 小鼠进行比较。从治疗前到治疗后,老年对照组小鼠的收缩压升高,但吡哆胺治疗组小鼠的收缩压保持不变。吡哆胺治疗组小鼠的大动脉僵硬程度降低,但对照组小鼠的大动脉僵硬程度没有变化。与老年对照组小鼠相比,吡哆胺治疗组小鼠的大脑动脉内皮依赖性扩张更大,与年轻小鼠无差异。老年对照组小鼠的认知功能受损;然而,吡哆胺仅部分保留了老年小鼠的认知功能。综上所述,吡哆胺治疗可预防老年小鼠血压升高、大动脉僵硬、脑动脉内皮功能障碍和认知功能障碍。综上所述,这些结果表明吡哆胺治疗可能限制血管老化。