Partial bladder obstruction secondary to benign prostatic hyperplasia is associated with increased bladder mass, alterations in bladder capacity, in bladder compliance and in in vitro responses to pharmacological stimulations. In the rabbit, the obstruction-induced changes in the bladder mass and function stabilized after 14 days. In the compensated period, alterations in biochemical parameters such as lactic acid, CO2 production and pyruvate metabolism and Krebs cycle enzyme activities indicate that mitochondrial energy production is affected. While physiological and biochemical changes of the obstructed bladder have been characterized, few studies of molecular mechanisms underlying these alterations have been attempted. The investigators have shown that in the first 14 days post obstruction, the relative number of copies of the mitochondrial genome decreases by 10-fold in the rabbit bladder; while TCA cycle enzymes decline in activity, cytochrome oxidase does not. Furthermore, although mitochondrial genome copy number decreases, mitochondrial transcript remains near normal, suggesting an upregulation of mitochondrial transcription in the compensated period. In the present proposal, the investigators plan to define alterations in expression for mitochondrial and nuclear genes during the compensated and decompensated periods after partial obstruction in rabbit. They also plan to correlate the molecular findings with urodynamic status, bladder mass, and the contractile responses to autonomic agonists, field stimulation and KCl. These studies will increase understanding of the molecular basis for bladder dysfunction after obstruction and may provide useful information for designing new therapeutic tools.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK047949-02
Application #
2444098
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1996-07-26
Project End
1997-08-31
Budget Start
1997-08-20
Budget End
1997-08-31
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Allegheny University of Health Sciences
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19129
Levin, Robert M; Hudson, Alan P (2004) The molecular genetic basis of mitochondrial malfunction in bladder tissue following outlet obstruction. J Urol 172:438-47
Ghafar, Mohamed A; Anastasiadis, Aristotelis G; Olsson, L Eric et al. (2002) Hypoxia and an angiogenic response in the partially obstructed rat bladder. Lab Invest 82:903-9
Ghafar, Mohamed A; Shabsigh, Ahmad; Chichester, Paul et al. (2002) Effects of chronic partial outlet obstruction on blood flow and oxygenation of the rat bladder. J Urol 167:1508-12
Wu, Xingyao; Wang, Zhao; Levin, Robert M et al. (2002) Cloning of COX4 cDNA from the NZ white rabbit and expression of this gene in bladder smooth muscle following partial outlet obstruction. World J Urol 20:255-9
Schroder, A; Kogan, B A; Lieb, J et al. (2001) Increased blood flow after catheterization and drainage in the chronically obstructed rabbit urinary bladder. Urology 58:295-300
Schroeder, A; Lieb, J; O'Connor, L et al. (2001) Role of calcium and calcium modulation in the control of urethral tone. Scand J Urol Nephrol Suppl :19-25; discussion 106-25
Bratslavsky, G; Kogan, B; Levin, R M (2001) Urethra is more sensitive to ischemia than bladder: evidence from an in vitro rat study. J Urol 165:2086-90
Schroder, A; Levin, R M; Kogan, B A et al. (2001) Aspirin treatment improves bladder function after outlet obstruction in rabbits. Urology 58:608-13
Wang, Z; Wu, X; Levin, R M et al. (2001) Loss of mitochondrial DNA in rabbit bladder smooth muscle following partial outlet obstruction results from lack of organellar DNA replication. Mol Urol 5:99-104
Parekh, M H; Lobel, R; O'Connor, L J et al. (2001) Protective effect of vitamin E on the response of the rabbit bladder to partial outlet obstruction. J Urol 166:341-6

Showing the most recent 10 out of 28 publications