Urinary incontinence (UI) constitutes a major health problem in the elderly population and represents the second leading casue of admission to nursing homes. The proposed research is based upon the working hypothesis that alterations in the responsiveness of the urinary bladder to normal physiological autonomic nervous system influences contribute to the pathophysiology of some types of UI. Experiments will be conducted in isolated intact and in situ bladders and in isolated detrusor (dome) and sphincter + trigone (neck) preparations obtained from F344 rats 6, 15-16, and 26-28 mo. Studies will be designed to determine whether there are age-related alterations in sensitivity to contractions induced by cholinergic and alpha- and beta-adrenergic agents. Where such sensitivity changes occur, studies will be conducted to determine their mechanistic basis and will include: receptor binding characteristics; post-receptor changes in adenylate cyclase; and changes in neurotransmitter concentrations and rates of synthesis and release. Pilot studies will determine whether age-related changes in bladder sensitivity develop to selected prostaglandins and to ATP. These results are of great potential biomedical and clinical significance: (1) To characterize the autonomic receptors of the rat bladder dome and neck and determine the adrenoceptor subtypes. (2) To better understand alterations in tissue sensitivity to cholinergic and adrenergic agents that occur with aging and detemine the mechanistic basis for such changes. These results have direct applicability to bladder function and are of general significance in the study of tissues receiving autonomic innervation. (3) To investigate possible autonomic involvement in the pathogenesis of UI in aging and develop a more rational and safer basis for its management. (4) A large and diverse number of drugs have potential effects on lower urinary tract function (urine storage and expulsion). These results may assist in the prediction of adverse drug effects or drug interactions on the lower urinary tract of elderly individuals.
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