Pathologic conditions, primarily obstruction, result in changes in ureteral length and diameter, which in turn affects the ability of the ureter to contract. Abnormalities in ureteral function may in turn lead to deterioration of renal structure and function. In addition, preliminary data have suggested that there are age dependent changes in the ureter that in themselves effect its function and that influence its response to obstruction. As an example, it is apparent clinically that obstruction results in more extensive ureteral dilatation in the neonate than in the adult. Furthermore, we have demonstrated that the neonatal rabbit ureter undergoes greater dimensional deformation in response to obstruction and has a greater sensitivity to neurohumoral agents, i.e., catacholamines, than does the adult rabbit ureter. Thus there are apparent differences in the structure and pharmacologic responses of the neonatal and adult ureter which affect their ability to function. The full extent of and reason for these age dependent variations in ureteral mechanical and pharmacological properties is not known. It is plnned to define the age related changes in the mechanical properties, and pharmacologic responses of the neonatal, adult, and elderly adult ureter. The effects of age on the interrelationships of intraluminal pressure, wall tension, length and diametral deformation, and the force and velocity of contraction will be determined. In addition, changes in the pharmacologic properties, i.e. response to neurohumoral agents, catecholamine content, endogenous cAMP levels and adenylate cyclase and phosphodiesterase activity, as affected by aging and disease will be investigated. It is hoped that this information concerning ureteral smooth muscle may give insight into methods of management of the ureter in pathologic conditions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK038311-12
Application #
3237606
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1977-02-01
Project End
1990-08-31
Budget Start
1989-09-01
Budget End
1990-08-31
Support Year
12
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
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Yono, Makoto; Pouresmail, Mehdi; Takahashi, Wataru et al. (2005) Effect of insulin treatment on tissue size of the genitourinary tract in BB rats with spontaneously developed and streptozotocin-induced diabetes. Naunyn Schmiedebergs Arch Pharmacol 372:251-5
Yono, Makoto; Foster Jr, Harris E; Shin, David et al. (2005) Molecular classification of doxazosin-induced alterations in the rat prostate using gene expression profiling. Life Sci 77:470-9
Wheeler, Marcia A; Ayyagari, Rajasekhara R; Wheeler, George L et al. (2005) Regulation of cyclic nucleotides in the urinary tract. J Smooth Muscle Res 41:1-21
Yono, Makoto; Latifpour, Jamshid; Takahashi, Wataru et al. (2004) Age-related changes in the properties of the endothelin receptor system at protein and mRNA levels in the rat vas deferens. J Recept Signal Transduct Res 24:53-66
Foster Jr, Harris E; Yono, Makoto; Shin, David et al. (2004) Effects of chronic administration of doxazosin on alpha1-adrenoceptors in the rat prostate. J Urol 172:2465-70

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