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 PO2 and/or acidosis-induced ATP release front 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 Cite. 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 PO, and/or acidosis. Extraluminally applied ATP causes constriction (via smooth muscle cell P-2X1 receptor) with subsequent dilation (via endothelial P-2Y2 Stimulation), 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 PO2 causes 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. (C) 2002 Elsevier Science B.V. All rights reserved.