ArticleCirculation research2012
Impaired skeletal muscle blood flow control with advancing age in humans: attenuated ATP release and local vasodilation during erythrocyte deoxygenation.
Article in Circulation research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
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Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 102 citations in OpenAlex.
- Effects of physical exercise on the functionality of human nucleotidases: A systematic review.Physiological reports · 2022Pooled it
- Rho-kinase inhibition improves haemodynamic responses and circulating ATP during hypoxia and moderate intensity handgrip exercise in healthy older adults.The Journal of physiology · 2022Trial
- Amplification of endothelium-dependent vasodilatation in contracting human skeletal muscle: role of KThe Journal of physiology · 2019Trial
- Plasma Nucleotide Dynamics during Exercise and Recovery in Highly Trained Athletes and Recreationally Active Individuals.BioMed research international · 2018Trial
- Acute effect of dietary nitrate on forearm muscle oxygenation, blood volume and strength in older adults: A randomized clinical trial.PloS one · 2017Trial
- Aging is associated with altered vasodilator kinetics in dynamically contracting muscle: role of nitric oxide.Journal of applied physiology (Bethesda, Md. : 1985) · 2015Trial
- Acute ascorbic acid ingestion increases skeletal muscle blood flow and oxygen consumption via local vasodilation during graded handgrip exercise in older adults.American journal of physiology. Heart and circulatory physiology · 2015Trial
- Acute dietary nitrate supplementation enhances compensatory vasodilation during hypoxic exercise in older adults.Journal of applied physiology (Bethesda, Md. : 1985) · 2015Trial
- Human red blood cell ATP content and export under hypoxic and/or isocapnic storage conditions.Frontiers in physiology · 2025Article
- Effect of low-dose terazosin on arterial stiffness improvement: A pilot study.Journal of cellular and molecular medicine · 2024Article
- Metabolomic analysis of dietary-restriction-induced attenuation of sarcopenia in prematurely aging DNA repair-deficient mice.Journal of cachexia, sarcopenia and muscle · 2024Article
- Article
- Age-related impairments in ATP release by red blood cells as an important contributor to declines in skeletal muscle blood flow in older adults.The Journal of physiology · 2022Article
- Optimized HPLC method to elucidate the complex purinergic signaling dynamics that regulate ATP, ADP, AMP, and adenosine levels in human blood.Purinergic signalling · 2022Article
- Matching of OFrontiers in physiology · 2022Review
- ATP and acetylcholine interact to modulate vascular tone and αJournal of applied physiology (Bethesda, Md. : 1985) · 2021Article
- Pannexin 1 channels control the hemodynamic response to hypoxia by regulating OAmerican journal of physiology. Heart and circulatory physiology · 2021Article
- Generation and Export of Red Blood Cell ATP in Health and Disease.Frontiers in physiology · 2021Review
- KThe Journal of physiology · 2020Article
- A Translational In Vivo and In Vitro Metabolomic Study Reveals Altered Metabolic Pathways in Red Blood Cells of Type 2 Diabetes.Journal of clinical medicine · 2020Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
rationaleSkeletal muscle blood flow is coupled with the oxygenation state of hemoglobin in young adults, whereby the erythrocyte functions as an oxygen sensor and releases ATP during deoxygenation to evoke vasodilation. Whether this function is impaired in humans of advanced age is unknown.
objectiveTo test the hypothesis that older adults demonstrate impaired muscle blood flow and lower intravascular ATP during conditions of erythrocyte deoxygenation. METHODS AND
resultsWe showed impaired forearm blood flow responses during 2 conditions of erythrocyte deoxygenation (systemic hypoxia and graded handgrip exercise) with age, which was caused by reduced local vasodilation. In young adults, both hypoxia and exercise significantly increased venous [ATP] and ATP effluent (forearm blood flow×[ATP]) draining the skeletal muscle. In contrast, hypoxia and exercise did not increase venous [ATP] in older adults, and both venous [ATP] and ATP effluent were substantially reduced compared with young people despite similar levels of deoxygenation. Next, we demonstrated that this could not be explained by augmented extracellular ATP hydrolysis in whole blood with age. Finally, we found that deoxygenation-mediated ATP release from isolated erythrocytes was essentially nonexistent in older adults.
conclusionsSkeletal muscle blood flow during conditions of erythrocyte deoxygenation was markedly reduced in aging humans, and reductions in plasma ATP and erythrocyte-mediated ATP release may be a novel mechanism underlying impaired vasodilation and oxygen delivery during hypoxemia with advancing age. Because aging is associated with elevated risk for ischemic cardiovascular disease and exercise intolerance, interventions that target erythrocyte-mediated ATP release may offer therapeutic potential.
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