Rabbit erythrocytes release ATP and dilate skeletal muscle arterioles in the presence of reduced oxygen tension

In skeletal muscle, oxygen (O2) delivery to appropriately meet metabolic need requires mechanisms for detection of the magnitude of O2 demand and the regulation of O2 delivery. Erythrocytes, when exposed to a decrease in O2 tension, release both O2 and the vasodilator adenosine triphosphate (ATP). The aims of this study were to establish that erythrocytes release ATP in response to reduced O2 tension and determine if erythrocytes are necessary for the dilation of isolated skeletal muscle arterioles exposed to reduced extraluminal O2 tension. Rabbit erythrocytes exposed to reduced O2 tension in a tonometer (n = 5, pO2 = 27 ± 3, p < 0.01) released ATP in response to reduced O2 tension. ATP release increased in proportion to the decrease in O2 tension. The contribution of erythrocytes to the response of skeletal muscle arterioles to reduced extraluminal O2 tension was determined using isolated hamster cheek pouch retractor muscle arterioles perfused with buffer (n = 11, mean diameter 52 ± 3 μm) in the absence and presence of rabbit erythrocytes. Without erythrocytes, arterioles did not dilate when exposed to reduced extraluminal O2 tension (pO2 = 32 ± 4 mmHg). In contrast, when rabbit erythrocytes were present in the perfusate (hematocrit 15%), the same decrease in O2 tension resulted in a 20 ± 4% dilation (p < 0.01). These results provide support for the hypothesis that erythrocytes, via their ability to release O2 along with ATP in response to exposure to reduced O2 tension, can participate in the matching of O2 delivery with metabolic need in skeletal muscle.