Abstract 13005: Temperature Sensitive Erythrocyte ATP Release: A Mechanism of Enhancing Human Limb Tissue Blood Flow
Human limb muscle and skin perfusion increases profoundly with elevations in tissue temperature evoked by heat stress and/or exercise, a process that might involve temperature sensitive regulatory mechanisms. Here we tested the hypothesis that the release of the vasodilator and sympatholytic mediator ATP from human erythrocytes is sensitive to physiological increases in temperature both in vivo and in situ, and examined potential pathways involved. In 10 healthy subjects exposed to progressive whole body heat stress where quadriceps muscle temperature increased from 36.4 ± 0.3°C to 38.5 ± 0.2°C at rest and from 38.5 ± 0.3°C to 40.2 ± 0.2°C with one-legged knee extensor exercise, increases in arterial plasma ATP strongly correlated with elevations in muscle temperature (r2= 0.91; P<0.05). To investigate the blood source of ATP release, whole blood, red blood cells (RBC), plasma and serum were heated in situ to physiological muscle temperatures (i.e., 33°C, 36°C, 39°C and 42°C). As with our in vivo findings, in situ heating augmented plasma ATP from whole blood from 1078 ± 88 nmoln·l−1 at 33°C to 1573 ± 166 nmol·l−1 at 42°C (n=7, P=0.08) while there was no change in either isolated plasma or serum samples. ATP release from RBC also increased incrementally from 785 ± 114 nmol·l−1 at 33°C to 3535 ± 468 nmol·l−1 at 42°C (n=10, P<0.01), indicating that erythrocytes were the sole source of temperature induced elevations in ATP. Erythrocyte ATP release at 39°C was completely blocked with 400 μmol·l−1 niflumic acid (a non-specific ion channel inhibitor; n =6, P<0.01), attenuated by 60 ± 9% with 400 μmol·l−1 glibenclamide (a specific blocker of cystic fibrosis transmembrane regulator (CFTR); n=7, P<0.05), only blocked by 10 ± 4% with an inhibitor of nucleoside transport and not affected by an anion exchange inhibitor. Our findings demonstrate that erythrocyte ATP release is sensitive to physiological increases in temperature, possibly via activation of CFTR like channels. Moreover they imply that increasing limb muscle temperatures in patients with peripheral vascular disease or paralysed muscle could improve local blood flow and oxygen and substrate supply via non-pharmacological stimulation of erythrocyte ATP release.
- © 2010 by American Heart Association, Inc.