DESCRIPTION (Applicant's abstract):Occlusion of the femoral artery in rats is a reasonable model of peripheral artery disease in humans. In the absence of exogenous growth factors, there is a minimal increase in collateral-dependent blood flow in response to occlusion. When exogenous VEGF or bFGF is given there is dramatic improvement in collateral-dependent blood flow. The improved collateral-dependent blood flow is specific to the occluded side and can be abolished by giving NOS inhibitors with exogenous growth factors. The overall goal of this project is to identify changes that establish the responsiveness of collateral vessels to external stimuli. The specific aims are: 1) Identify potential mediators of the collateral remodeling response in the absence of intervention and after growth factor treatment, 2) establish mediators of the collateral response that are modulated by moderate exercise, and 3) establish mediators of the growth factor-induced collateral response that are modulated by L-NAME treatment. Rats will be unilaterally ligated and given intra-arterial infusion of vehicle, VEGF or bFGF. L-NAME will be given via drinking water. At the optimal time after the start of treatment, rats, in groups of six or twelve, will be euthanized and collateral vessels harvested bilaterally for biochemical and RT-PCR analysis. It is anticipated that these results will form a basis for effective treatment of peripheral vascular disease using exogenous growth factors.