The Age-Old Tale of Skeletal Muscle Vasodilation: New Ideas Regarding Erythrocyte Dysfunction and Intravascular ATP in Human Physiology

To the Editor: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 small-muscle 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 …