November 28, 2002Open Access
View Full PaperErythrocyte and the Regulation of Human Skeletal Muscle Blood Flow and Oxygen Delivery
Key Result
Venous ATP levels during exercise were tightly correlated with alterations in venous (O2+CO)Hb (r2=0.93 to 0.96; P<0.01), supporting the role of erythrocytes as oxygen sensors regulating blood flow.
Structured PICO
Does the erythrocyte regulate skeletal muscle blood flow and oxygen delivery by releasing ATP depending on hemoglobin oxygenation?
P
Population
8 young subjects undergoing incremental one-legged knee-extensor exercise under conditions of normoxia, hypoxia, hyperoxia, and CO+normoxia.
I
Intervention
Incremental one-legged knee-extensor exercise under conditions of normoxia, hypoxia, hyperoxia, and CO+normoxia; intrafemoral artery infusion of ATP at rest in normoxia (n=5)
C
Comparator
Different oxygenation states (normoxia, hypoxia, hyperoxia, CO+normoxia)
O
Outcome
Thigh blood flow (TBF), thigh vascular conductance (TVC), and femoral venous plasma [ATP]surrogate
The study supports the hypothesis that erythrocytes function as oxygen sensors, regulating skeletal muscle blood flow by releasing ATP based on unoccupied oxygen binding sites on hemoglobin.
Main Result
Effect estimate: r2=0.93 to 0.96
p-value: p=<0.01
Abstract
Blood flow to contracting skeletal muscle is tightly coupled to the oxygenation state of hemoglobin. To investigate if ATP could be a signal by which the erythrocyte contributes to the regulation of skeletal muscle blood flow and oxygen (O2) delivery, we measured circulating ATP in 8 young subjects during incremental one-legged knee-extensor exercise under conditions of normoxia, hypoxia, hyperoxia, and CO+normoxia, which produced reciprocal alterations in arterial O2 content and thigh blood flow (TBF), but equal thigh O2 delivery and thigh O2 uptake. With increasing exercise intensity, TBF, thigh vascular conductance (TVC), and femoral venous plasma ATP augmented significantly (P<0.05) in all conditions. However, with hypoxia, TBF, TVC, and femoral venous plasma ATP were (P<0.05) or tended (P=0.14) to be elevated compared with normoxia, whereas with hyperoxia they tended to be reduced. In CO+normoxia, where femoral venous O2Hb and (O2+CO)Hb were augmented compared with hypoxia despite equal arterial deoxygenation, TBF and TVC were elevated, whereas venous ATP was markedly reduced. At peak exercise, venous ATP in exercising and nonexercising limbs was tightly correlated to alterations in venous (O2+CO)Hb (r2=0.93 to 0.96; P<0.01). Intrafemoral artery infusion of ATP at rest in normoxia (n=5) evoked similar increases in TBF and TVC than those observed during exercise. Our results in humans support the hypothesis that the erythrocyte functions as an O2 sensor, contributing to the regulation of skeletal muscle blood flow and O2 delivery, by releasing ATP depending on the number of unoccupied O2 binding sites in the hemoglobin molecule.