Although there have been a number of studies on experimental bladder outlet obstruction, the majority of them have been of limited scope. This section of the proposed study will systematically evaluate the in vitro functional and biochemical changes that result from bladder outlet obstruction of varying magnitude and duration, and specifically evaluate the following parameters in obstructed vs normal cats: (1) in vitro cystometry and the functional ability of the bladder to empty; (2) secondary changes in ureteral function and biochemistry; (3) contractility of isolated strips of bladder dome, body, base and urethra; (4) correlation of the contractile response of the strips to specific adrenergic and cholinergic agonists with specific autonomic receptors densities as determined by radioligand receptor analysis; and (5) intracellular concentrations of ATP, CP, DNA, RNA, lipids, glycogen, elastin and collagen. The results will be correlated with data obtained from in vivo studies (Section I) and morphologic/morphometric evaluation of the bladder and ureter (Section II), in order to determine the pathogenetic mechanism(s) responsible for vesical and ureteral dysfunction in obstructive uropathy.
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