One of the current main concerns of the discipline of clinical urology is the accurate diagnosis and optimal treatment of obstructive uropathy. It is well known that urethral obstruction can lead to ureteral dysfunction, and eventually to deterioration of renal function. Yet, precise knowledge of the mechanisms by which the commonest cause of clinical obstructive uropathy (namely, vesical outlet obstruction) alters vesical, ureteral and ultimately renal function is still lacking.
The specific aim of this proposal is to define the pathogenetic mechanisms of vesical, ureteral and renal dysfunctions in obstructive uropathy, by integrated functional, morphologic and biochemical studies. In this proposal, a valid quantifiable cat model of urethral obstruction will be created. Two models are planned in this proposal: one of a high-grade, and another of a milder and more gradually developing """"""""obstruction"""""""". Once obstruction has developed and been characterized urodynamically in both models, subsequent study of the neuromuscular structure, the in vitro contractility, autonomic receptor densities, pharmacologic responses, and biochemical profile of the detrusor and ureteral muscularis will be correlated with their in vivo function, to define the mechanism(s) of obstructive vesical and ureteral dysfunctions. Subsequently, the relation of a certain degree of infravesical obstruction to renal functional parameters - including renal blood flow, tubular function, renal secretory products and glomerular filtration - will be defined. Morphologic changes in the renal parenchyma will also be defined and correlated with functional parameters.
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