The long-range goals of the PI are to evaluate the mechanisms that regulate blood flow delivery during exercise. The short-range goal of this proposal is to examine the role muscle metabolites play in evoking the exercise pressor reflex. Specifically, prior studies examining the metabolic engagement of this skeletal muscle reflex have not characterized interstitial concentrations of many of the putative metabolic stimulants. This remains an important concern since the free endings of the afferent nerves in question reside within the muscle interstitium. In this proposal, a decerebrate, unanesthetized, cat model will be used to further characterize the effects of interstitial metabolites on the muscle reflex. These experiments utilize microdialysis techniques to characterize interstitial concentrations of a number of potential metabolic stimulants. Specifically, we will utilize microdialysis to measure the interstitial concentrations of lactate, hydrogen ion, potassium, phosphate and adenosine. These measurements will be performed under two separate experimental conditions: 1) during a rhythmic contraction paradigm illicited with a variable amplitude and frequency stimulator as blood pressure, heart rate, renal sympathetic nerve activity and muscle sympathetic nerve activity are measured, and 2) in a separate group of experiments, the circulation to the cat hindlimb will be isolated and perfused with many of these various potential stimulants as interstitial measurements are made and reflex responses are measured. We believe these studies may help us further understand the role various metabolites play in evoking the muscle reflex. Novel components of the work described include the use of microdialysis to measure multiple interstitial metabolites, the use of a decerebrate preparation, the use of rhythmic contraction paradigms, and the use of an isolated hindlimb perfusion system.
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