ATP - THE RED-BLOOD-CELL LINK TO NO AND LOCAL-CONTROL OF THE PULMONARY CIRCULATION

Recently, we reported that rabbit red blood cells (RBCs) were required for the expression of nitric oxide (NO) activity on pulmonary vascula r resistance (PVR) in rabbit lungs. Here, we investigate the hypothesi s that RBCs participate in the regulation of PVR via release of ATP in response to mechanical deformation that, in turn, evokes vascular NO synthesis. We found that rabbit and human RBCs, but not dog RBCs, rele ase ATP in response to mechanical deformation. To determine the contri bution of this ATP to NO synthesis and PVR, we compared the effects of human and dog RBCs on pressure-flow relationships in isolated rabbit lungs. In the presence of human RBCs, N-G-nitro-L-arginine methyl este r (100 mu M) produced a shift in the pressure-flow relationship consis tent with a reduction in vascular caliber. N-G-nitro-L-arginine methyl ester had no effect in lungs perfused with dog RBCs. These results su ggest a unique mechanism for the control of PVR in rabbits and humans whereby release of ATP by RBCs in response to mechanical deformation l eads to stimulation of NO synthesis that, in turn, modulates the PVR.