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 on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG000112-08
Application #
3114036
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1977-02-01
Project End
1986-08-31
Budget Start
1985-09-01
Budget End
1986-08-31
Support Year
8
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
Cho, Y H; Wheeler, M A; Weiss, R M (1988) Ontogeny of cyclic AMP and cyclic GMP phosphodiesterase activities and of calmodulin levels in guinea pig ureter. J Urol 139:1095-8
Morita, T; Wada, I; Saeki, H et al. (1987) Ureteral urine transport: changes in bolus volume, peristaltic frequency, intraluminal pressure and volume of flow resulting from autonomic drugs. J Urol 137:132-5
Morita, T; Wheeler, M A; Weiss, R M (1987) Age-related changes in contractile force of rabbit detrusor muscle to prostaglandin E1, E2 and F2 alpha. Urol Int 42:44-8
Morita, T; Latifpour, J; O'Hollaren, B et al. (1987) Sex differences in function and distribution of alpha 1- and alpha 2-adrenoceptors in rabbit urethra. Am J Physiol 252:F1124-8
Morita, T; Wheeler, M A; Weiss, B M et al. (1986) [Effects of dobutamine and terbutaline on isometric force of rabbit pelvi-ureteral smooth muscle strips] Nippon Hinyokika Gakkai Zasshi 77:501-6
Morita, T; Wheeler, M A; Weiss, R M (1986) Relaxant effect of forskolin in rabbit detrusor smooth muscle: role of cyclic AMP. J Urol 135:1293-5
Wheeler, M A; Housman, A; Cho, Y H et al. (1986) Age dependence of adenylate cyclase in guinea pig ureter homogenate. J Pharmacol Exp Ther 239:99-103
Morita, T; Wheeler, M A; Weiss, R M (1986) Effects of noradrenaline, isoproterenol and acetylcholine on ureteral resistance. J Urol 135:1296-8
Morita, T; Wheeler, M; Weiss, R M et al. (1986) [Effect of beta-adrenoceptor agonists of the spontaneous contractility of isolated rabbit urinary bladder muscle strips] Nippon Hinyokika Gakkai Zasshi 77:226-32
Morita, T; Wheeler, M A; Weiss, R M (1986) Sphincteric action of the pelvicalyceal junction and pacemaker activity in human kidney. Urol Int 41:167-9

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