Micturition is a complex neuromuscular process. Although control mechanisms have been identified at several levels of the central nervous system and spinal cord, the final pathway in the control of micturition is the autonomic innervation of the urinary bladder and related structures. Our general research objective is to identify specific alterations in bladder function, physiology, and morphology which relate to specific urogenital conditions. Studies to date indicate that the bladder reacts to several experimental pathologies and specific surgical manipulations with rapid compensatory changes in both bladder function and structure. The major objective of the current proposal is to systematically characterize and correlate the physiological, functional, and morphological responses of the bladder to chronic outlet obstruction, removal of the outlet obstruction, and subtotal cystectomy. The emphasis of these proposed studies will be n the compensatory mechanisms by which the bladder responds and adapts to outlet obstruction, relief of outlet obstruction, and subtotal cystectomy. An understanding of the progression of these models will help in understanding the extent to which the bladder can compensate in response to specific challenges, and, determine if and when intervention should take place. The progressive response of the bladder to the above experimental conditions will be monitored using a variety of research methodologies. These methods will quantitate and correlate the functional, biochemical and morphologic changes in the bladder. Functional changes will be assessed by: 1) measurements of volume and frequency of voiding; 2) in vivo cystometry; 3) evaluation of the ability of the in-vitro bladder to generate pressure and empty in response to electrical field stimulation,muscarinic, and purinergic stimulation; and 4) determination of the distribution and density of the various autonomic receptors. Biochemical assays will determine collagen and elastin content and distribution, and the tissue content and concentration of ATP, CP, DNA and RNA. Morphologic changes will be determined by detailed morphometric studies of the bladder body and base. Data to be collected by the three modalities of study will be analyzed statistically by the appropriate methods, and correlated in relation to bladder storage/voiding function in the various experimental settings.
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