DIABETES INDUCED DECREASE IN DETRUSOR SMOOTH MUSCLE FORCE IS ASSOCIATED WITH OXIDATIVE STRESS AND OVERACTIVITY OF ALDOSE REDUCTASE
2005; Lippincott Williams & Wilkins; Volume: 173; Issue: 1 Linguagem: Inglês
10.1097/01.ju.0000141583.31183.7a
ISSN1527-3792
AutoresArun Changolkar, Joseph Hypolite, Michael E. DiSanto, Peter J. Oates, Alan J. Wein, Samuel Chacko,
Tópico(s)Heme Oxygenase-1 and Carbon Monoxide
ResumoNo AccessJournal of UrologyInvestigative Urology1 Jan 2005DIABETES INDUCED DECREASE IN DETRUSOR SMOOTH MUSCLE FORCE IS ASSOCIATED WITH OXIDATIVE STRESS AND OVERACTIVITY OF ALDOSE REDUCTASE ARUN K. CHANGOLKAR, JOSEPH A. HYPOLITE, MICHAEL DISANTO, PETER J. OATES, ALAN J. WEIN, and SAMUEL CHACKO ARUN K. CHANGOLKARARUN K. CHANGOLKAR , JOSEPH A. HYPOLITEJOSEPH A. HYPOLITE , MICHAEL DISANTOMICHAEL DISANTO , PETER J. OATESPETER J. OATES , ALAN J. WEINALAN J. WEIN , and SAMUEL CHACKOSAMUEL CHACKO View All Author Informationhttps://doi.org/10.1097/01.ju.0000141583.31183.7aAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Bladder dysfunction is one of the complications of diabetes. We determined whether diabetic induced bladder dysfunction is associated with decreased detrusor smooth muscle contractility, hyperglycemia induced over expression of aldose reductase (AR) and increased sorbitol production. In addition, we compared oxidative stress in the detrusor smooth muscle in diabetic rabbits with that in normal rabbits by estimating lipid peroxidation. Materials and Methods: Diabetes was induced in New Zealand White, age matched male rabbits by intravenous injection of alloxan (100 mg/kg body weight). Normal and sucrose drinking rabbits served as controls. Six months after the induction of diabetes rabbits with a blood glucose level of 400 mg/dl or higher were sacrificed and detrusor smooth muscle tissue was isolated. Detrusor was analyzed for force generation, lipid peroxidation products using malondialdehyde as a biomarker, and AR expression and function by reverse transcriptase-polymerase chain reaction and sorbitol levels, respectively. Results: The mean maximum force ± SE produced by detrusor muscle strips in response to 125 mM KCl was 17.50 ± 1.66, 17.56 ± 1.23 and 7.51 ± 2.56 gm/100 mg tissue in normal, sucrose drinking and diabetic rabbits, respectively, representing a 57% force decrease in diabetic subjects. Bethanechol elicited force decreased 40% (26.52 ± 3.21, 27.3 ± 2.87 and 16.32 ± 1.67 gm/100 mg tissue, respectively, in normal, sucrose drinking and diabetic rabbits) in diabetic vs control subjects. Concomitant with the force decrease, the expression of AR, sorbitol content and lipid peroxidation products were increased. Conclusions: Diabetes induced a decrease in detrusor smooth muscle force. This was associated with an increase in lipid peroxides and sorbitol concomitant with over expression of AR and polyol pathway activation. Our data suggest that these changes might contribute to oxidative stress and decreased contractility of detrusor smooth muscle, leading to bladder dysfunction. 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Google Scholar From the Division of Urology (AKC, JAH, MD, AJW, SC), Department of Pathobiology (AKC, SC), University of Pennsylvania, Philadelphia, Pennsylvania, and Department of Cardiovascular and Metabolic Diseases, Pfizer Global Research and Development (PJO), Groton, Connecticut© 2005 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byWein A (2018) Re: Bladder Function in Mice with Inducible Smooth Muscle-Specific Deletion of the Manganese Superoxide Dismutase GeneJournal of Urology, VOL. 197, NO. 1, (219-220), Online publication date: 1-Jan-2017.Xiao N, Wang Z, Huang Y, Daneshgari F and Liu G (2018) Roles of Polyuria and Hyperglycemia in Bladder Dysfunction in DiabetesJournal of Urology, VOL. 189, NO. 3, (1130-1136), Online publication date: 1-Mar-2013.Lee W, Chuang Y, Chiang P, Chien C, Yu H and Wu C (2018) Pathophysiological Studies of Overactive Bladder and Bladder Motor Dysfunction in a Rat Model of Metabolic SyndromeJournal of Urology, VOL. 186, NO. 1, (318-325), Online publication date: 1-Jul-2011.Daneshgari F, Leiter E, Liu G and Reeder J (2009) Animal Models of Diabetic UropathyJournal of Urology, VOL. 182, NO. 6S, (S8-S13), Online publication date: 1-Dec-2009.Daneshgari F, Liu G, Birder L, Hanna-Mitchell A and Chacko S (2009) Diabetic Bladder Dysfunction: Current Translational KnowledgeJournal of Urology, VOL. 182, NO. 6S, (S18-S26), Online publication date: 1-Dec-2009.MANNIKAROTTU A, CHANGOLKAR A, DISANTO M, WEIN A and CHACKO S (2018) OVER EXPRESSION OF SMOOTH MUSCLE THIN FILAMENT ASSOCIATED PROTEINS IN THE BLADDER WALL OF DIABETICSJournal of Urology, VOL. 174, NO. 1, (360-364), Online publication date: 1-Jul-2005. Volume 173Issue 1January 2005Page: 309-313 Advertisement Copyright & Permissions© 2005 by American Urological Association, Inc.Keywordsrabbitsmuscle contractiondiabetesbladdermuscle, smoothMetricsAuthor Information ARUN K. CHANGOLKAR More articles by this author JOSEPH A. HYPOLITE More articles by this author MICHAEL DISANTO More articles by this author PETER J. OATES More articles by this author ALAN J. WEIN More articles by this author SAMUEL CHACKO More articles by this author Expand All Advertisement PDF downloadLoading ...
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