The age-old tale of skeletal muscle vasodilation: new ideas regarding erythrocyte dysfunction and intravascular ATP in human physiology.
The age-old tale of skeletal muscle vasodilation: new ideas regarding erythrocyte dysfunction and intravascular ATP in human physiology.
复制标题
骨骼肌血管舒张的古老故事：关于人体生理学中红细胞功能障碍和血管内 ATP 的新想法。
DOI：
10.1161/circresaha.112.279356
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发表时间：
2012
影响因子：
20.1
通讯作者：
Kirby,BrettS
中科院分区：
文献类型：
--
作者：
Dinenno,FrankA;Kirby,BrettS
We are honored that Circulation Research highlighted our recent investigation1 with a companion Editorial article by Dr Chilian and colleagues. 2 This undoubtedly will bring further attention to the significant and assorted cardiovascular dysfunctions that accrue with advancing age in humans, and for this we are appreciative. As within all good scientific practice, the authors raise a few considerations that they feel are important to bear in mind when assessing our experimental design and the associated conclusions. In this letter, we aim to simply address some of the issues raised in the Editorial with the goal of providing the readers of the journal with relevant scientific references and ultimately allow independent assessment of our work, as well as the work of others in this field. A principal observation from our investigation was that healthy older adults demonstrated remarkably impaired skeletal muscle vasodilation during systemic hypoxia as well as smallmuscle mass exercise, which coincided with a lack of increased plasma [ATP] during these conditions compared with young adults. This was not explained by augmented ATP hydrolysis in whole blood but was clearly associated with an impaired ability of isolated erythrocytes to release ATP in response to deoxygenation. Together, these data are of the first to identify that aging per se results in less than optimal tissue oxygen delivery during states of substantial hemoglobin deoxygenation and further, that these states are associated with a lack of increase in the plasma levels of the powerful vasoactive molecule ATP. 3 To our knowledge, we are unaware of any other study demonstrating an inability to elevate plasma ATP in any at-risk clinical population under such conditions. As stated, it is not the validity of these data that the authors of the Editorial take caution with, but rather the approach of integrating our in vitro data with the in human findings. Further, it is clear that the authors question the theory that the erythrocyte may be an oxygen sensor and aids in the integrated regulation of tissue blood flow. 4–6 Although our study did not aim to prove this general theory, an excellent scientific foundation existed to set the stage for our integrative study on human aging. 4–10
