ATP as a mediator of erythrocyte-dependent regulation of skeletal muscle blood flow and oxygen delivery in humans.
Level 5 - mechanism / opinion, no new human data
Narrative review of human physiological mechanisms and signal transduction
PubMed 22711955 · doi:10.1113/jphysiol.2012.235002
What was done
This narrative review synthesized human physiological evidence on how red blood cells regulate skeletal muscle blood flow and oxygen delivery during dynamic exercise, focusing on the role of erythrocyte-derived adenosine triphosphate (ATP) as a primary metabolic sensing and signaling mediator.
What was found
Exercising muscle blood flow responds primarily to hemoglobin-bound oxygen rather than dissolved plasma oxygen, nearly doubling (from 260 to 460 ml min-1 100 g-1) during alterations in blood oxygen content to maintain stable oxygen delivery. Red blood cells release ATP in response to low oxygen, elevated temperature, decreased pH, hypercapnia, elevated shear stress, and mechanical deformation. Intravascular ATP acts directly (not via degradation products like adenosine) as a potent vasodilator with sympatholytic properties in human limb circulations, overcoming concurrent sympathetic vasoconstriction during exercise.
Why it matters
The review outlines how erythrocytes function as active metabolic sensors rather than passive oxygen carriers, coordinating local microvascular tone and tissue perfusion during muscular work.
Limits
As a narrative review, it lacks systematic search methodology, risk-of-bias evaluation, and pooled quantitative analyses. The abstract synthesizes general physiological findings without providing sample sizes, participant demographics, or detailed primary trial designs.
Cited by
- supports During intense dynamic exercise, red blood cells, blood vessels, and skeletal muscle release ATP and ADP, which act as potent vasodilators causing local functional sympatholysis.