The urinary bladder is a smooth muscle organ whose function is to collect and store urine (at low intravesical pressures); and then to periodically expel the urine via a highly coordinated sustained contraction. Similar to other smooth muscle organs, the contractile function of the bladder is mediated by energy generated via the metabolism of intracellular substrates and the efficient generation of metabolic energy. Any pathological process which interferes with intracellular substrate utilization and energy production would be expected to result in the serious impairment of bladder function. The proposed studies can be separated into three major areas: 1) Detailed studies on the relationship between intracellular energetics, metabolism and contraction in the normal bladder. These studies include a detailed analysis of the role of mitochondria in bladder metabolism and contractile function. 2) The effect of specific experimental pathologies (partial outlets obstruction, acute over distension, and supravesical diversion) on bladder biochemistry, metabolism, and how they relate to alterations in contraction and function. 3) Correlation of the biochemical and functional effects of the specific experimental pathologies with morphology, obtained through the detailed histological evaluation of both control and pathological models by light, fluorescence, and electron microscopy. Our long-range goal is to identify specific metabolic defects that can either cause specific bladder pathologies, or result from specific pathologies. The proposed studies are designed to generate specific new information on the relationship between bladder metabolism (energetics), bladder function, and bladder morphology. This information would be extremely valuable in increasing our understanding the biochemical, metabolic and functional changes that accompany the development of specific bladder pathologies.
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