The erythrocyte as a regulator of vascular tone

Local regulation of microvascular blood flow is a complex process in which the needs of the tissue must be communicated to the vasculature, enabling the appropriate matching of O-2 supply to demand. We hypothesize that the red blood cell is not only the major O-2 carrier but also serves as an O-2 sensor and affecter of changes in O-2 delivery via its release of ATP, which subsequently binds to P-2y receptors on the vascular endothelium, altering vessel caliber. Using the hamster as a model, we determined that the efflux of ATP from red blood cells after exposure to low-PO2 (PO2 = 17 +/- 6 mmHg) and low-pH (pH = 7.06 +/- 0.07) solutions was significantly (P < 0.01) greater than that after exposure to normoxic, normal pH (PO2 = 87 +/- 4; pH = 7.38 +/- 0.04) solutions, indicating that two factors that are associated with an impaired O-2 supply relative to demand increase the release of ATP from the red blood cell. To ascertain whether ATP alters vascular caliber, we applied 10(-6) M ATP intraluminally to arterioles of the retractor muscle, using a micropressure system. Vessel diameter increased 8 and 10%, 140 +/- 60 mu m upstream of the site of infusion after 50- and 500-ms pulses, respectively. Application of ATP to arteriolar and venular capillaries induced a 31 and 81% increase in red blood cell supply rate, respectively. These results support our hypothesis that the red blood cell. is more than just an O-2 carrier and has a direct role in the regulation of vascular tone.