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

• Published in: Circulation research Vol. 91; no. 11; pp. 1046 - 1055
• Main Authors: González-Alonso, José, Olsen, David B., Saltin, Bengt
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 29.11.2002; Lippincott; Lippincott Williams & Wilkins Ovid Technologies
• Subjects: Adenosine Triphosphate - administration & dosage; Adenosine Triphosphate - blood; Adenosine Triphosphate - physiology; Administration, Inhalation; Adult; Biological and medical sciences; Blood Flow Velocity - drug effects; Blood Flow Velocity - physiology; Carbon Monoxide - pharmacology; Carboxyhemoglobin - analysis; Carboxyhemoglobin - metabolism; Erythrocytes - physiology; Female; Femoral Artery - physiology; Fundamental and applied biological sciences. Psychology; Hemoglobins - analysis; Hemoglobins - metabolism; Humans; Hyperoxia - metabolism; Hypoxia - metabolism; Infusions, Intra-Arterial; Leg - blood supply; Leg - physiology; Male; Muscle, Skeletal - blood supply; Muscle, Skeletal - physiology; Oxygen - metabolism; Oxygen Consumption - physiology; Physical Exertion - physiology; Reference Values; Regional Blood Flow - drug effects; Regional Blood Flow - physiology; Striated muscle. Tendons; Vertebrates: osteoarticular system, musculoskeletal system; Physical exercise; Knee; Human; Red blood cell; Oxygen transfer; Environmental factor; Striated muscle; Blood flow; skeletal muscle blood flow; Blood cell; Regulation(control); erythrocytes; Extensor muscle; oxygen delivery; oxygen sensor; Hemodynamics; ATP
• ISSN: 0009-7330; 1524-4571; 1524-4571
• DOI: 10.1161/01.RES.0000044939.73286.E2

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 (r=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.