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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Specialized Center (P50)
Project #
5P50DK039257-03
Application #
3105862
Study Section
Diabetes and Digestive and Kidney Diseases Special Grants Review Committee (DDK)
Project Start
1987-09-01
Project End
1992-07-31
Budget Start
1989-08-01
Budget End
1990-07-31
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Upstate Medical University
Department
Type
Schools of Medicine
DUNS #
058889106
City
Syracuse
State
NY
Country
United States
Zip Code
13210
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Levin, R M; Monson, F C; Longhurst, P A et al. (1994) Rabbit as a model of urinary bladder function. Neurourol Urodyn 13:119-35
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Hess, M E; Barasha, B; Winters, S et al. (1993) Effect of thyroxine on urinary bladder autonomic receptor densities and contractility. Pharmacology 46:248-53
Samadzadeh, S; Tong, Y C; Wein, A J et al. (1992) Influence of the bathing medium on the contractile responses of the rabbit urinary bladder. Pharmacology 45:99-106
Longhurst, P A; Eika, B; Leggett, R E et al. (1992) Urinary bladder function in the tight-skin mouse. J Urol 148:1611-4
Bilgen, A; Wein, A J; Zhao, Y et al. (1992) Effects of anoxia on the biphasic response of isolated strips of rabbit bladder to field stimulation, bethanechol, methoxamine and KCl. Pharmacology 44:283-9
Levin, R M; Haugaard, N; Packard, D et al. (1992) Effect of ryanodine on mitochondrial respiration. Pharmacology 45:117-20
Tammela, T L; Wein, A J; Levin, R M (1992) Effect of tetrodotoxin on the phasic and tonic responses of isolated rabbit urinary bladder smooth muscle to field stimulation. J Urol 148:1937-40

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