Erythrocyte and the Regulation of Human Skeletal Muscle Blood Flow and Oxygen Delivery

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.