The overall objective of our research on skeletal muscle blood flow is identification of the mechanisms responsible for vasodilation associated with exercise. The major focus of this application is the role of endothelial cells in mediating the vasodilation of distributing arteries which are responsible for maintaining the pressure head to the microcirculation during exercise. We are also interested in the role of endothelial cells in the dilation and development of collateral vessels which supply the microcirculation when distributing arteries are occluded. We propose to elucidate the physiologic importance of endothelial cells in mediating the vasodilation of distributing arteries. Our goals are (a) to determine the physiologic role of distributing artery flow-dependent dilation in exercise hyperemia, (b) to further characterize the mechanism of flow-dependent dilation in the canine femoral artery, and (c) to determine the role of endothelial cells in the dilation and growth of collateral vessels during acute and chronic occlusion of the distributing artery. We will also examine the effect of heartworm (Dirofilaria immitis), a common filarial parasitic infection of domestic dogs, on endothelium-dependent vasodilation.