Erythrocyte and the Regulation of Human Skeletal Muscle Blood Flow and Oxygen Delivery: Role of Circulating ATP

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 (O 2 ) 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 O 2 content and thigh blood flow (TBF), but equal thigh O 2 delivery and thigh O 2 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 O 2 Hb and (O 2 +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 (O 2 +CO)Hb ( r 2 =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 O 2 sensor, contributing to the regulation of skeletal muscle blood flow and O 2 delivery, by releasing ATP depending on the number of unoccupied O 2 binding sites in the hemoglobin molecule.