The red blood cell, ATP and integrated vascular responses to neuronal stimulation

Purpose: To provide new insights for linking neuronal activation, local sensing of metabolic need and adenosine triphosphate (ATP) release from red blood cells to conducted vasomotor responses as a mechanism to regulate cerebral microvascular blood flow according to the local tissue needs as seen after, e.g., whisker barrel stimulation [J. Cereb. Blood Flow Metab. 13 (1993) 899]. Methods: We measured low PO₂and/or acidosis-induced ATP release from red blood cells. In isolated and pressurized rat-penetrating arterioles, we simulated neuronal ATP release with local microapplication to study local and conducted vasomotor responses [Am. J. Physiol.: Heart Circ. Physiol. 271 (1996) H1109]. In arterioles of hamster retractor muscle, we microinfused ATP to simulate ATP release from red blood cells. Finally, we measured low PO₂-induced ATP release in red blood cell-perfused cerebral arterioles. Results: Red blood cells release ATP in response to low PO₂and/or acidosis. Extraluminally applied ATP causes constriction (via smooth muscle cell P_2X1receptor) with subsequent dilation (via endothelial P_2Y2stimulation), with the dilation conducted along the vessel. Microinfused ATP causes retrogradely conducted vasodilation, which is blunted with high ATP doses. Only in red blood cell-perfused arterioles does low PO₂causes vasodilation coincident with an increase in ATP in the perfusate. Conclusion: Local release of ATP either from neurons or from red blood cells (as a sensor for oxygen need) or both may cause local microvascular vessel dilation which is conducted retrogradely to precisely adjust local microvascular flow to metabolic tissue need.