Blood flow in heart and skeletal muscle is normally modulated, by unknown local mechanisms, to follow changes in the metabolic needs of these tissues. The long-term goal of this work is to identify these mechanisms. Ultimately such knowledge would aid in the development of better therapeutic measures for correcting blood flow abnormalities in heart and skeletal muscle. It is currently hypothesized that muscle blood flow is regulated by an influence of interstitial adenosine concentration on the diameter of vessels within the tissue. The specific aims for this project are: 1) to establish the kinetics of each of the processes which remove adenosine from the interstitial space of muscle tissue, and 2) to apply this information in several tests of the hypothesis that adenosine mediates exercise hyperemia. A rat cremaster muscle preparation will be used to study arteriolar diameter response to topically-applied adenosine and to muscle exercise with a video-microscope system. In addition, HPLC techniques will be used to measure the adenosine concentration in solutions equilibrated with the surface of the muscle tissue. The microvascular observations, adenosine assay results, and a model of interstitial adenosine diffusion will be used together to make estimates of interstitial adenosine concentration and gradients in interstitial adenosine concentrations which exist in a variety of experimental situations. Specific experiments planned to determine: 1) the interstitial diffusion coefficient for adenosine, 2) the rate constants for adenosine removal from the interstitium by cellular uptake, interstitial degradation, and flow washout, and 3) the interstitial adenosine concentration which exists during different rates of muscle exercise.