Erythrocyte dependent regulation of human skeletal muscle blood flow: Role of varied oxyhemoglobin and exercise on nitrite, S-nitrosohemoglobin, and ATP

This study was funded by British Heart Foundation Grant PG/06/120 and American Heart Association Award 0355187. Article in press: Am J Physiol Heart Circ Physiol (September 17, 2010). doi: 10.1152/ajpheart.00389.2010 The final version of this article may be viewed at the link below.The erythrocyte is proposed to play a key role in the control of local tissue perfusion via three O₂-dependent signaling mechanisms: 1) reduction of circulating nitrite to vasoactive NO, 2), S-itrosohemoglobin (SNO-Hb)-dependent vasodilatation and 3) release of the vasodilator and sympatholytic ATP; however, their relative roles in vivo remain unclear. Here we evaluated each mechanism to gain insight into their roles in the regulation of human skeletal muscle blood flow during hypoxia and hyperoxia at rest and during exercise. Arterial and femoral venous hemoglobin O2 saturation (O₂Hb), plasma and erythrocyte NO and ATP metabolites and leg and systemic hemodynamics were measured in 10 healthy males exposed to graded hypoxia, normoxia and graded hyperoxia both at rest and during submaximal one-legged knee-extensor exercise. At rest, leg blood flow and NO and ATP metabolites in plasma and erythrocytes remained unchanged despite large alterations in O₂Hb. During exercise, however, leg and systemic perfusion and vascular conductance increased in direct proportion to decreases in arterial and venous O₂Hb (r²=0.86-0.98; P=0.01), decreases in venous plasma nitrite (r²2=0.93; P<0.01), increases in venous erythrocyte nitroso species (XNO) (r²=074; P