228 ALTERATION IN CAVEOLAR ELEMENTS AFFECTS BLADDER FUNCTIONAL RESPONSES IN ANIMAL MODELS OF DETRUSOR OVERACTIVITY

Abstract

You have accessJournal of UrologyBladder and Urethra: Anatomy, Physiology and Pharmacology1 Apr 2011228 ALTERATION IN CAVEOLAR ELEMENTS AFFECTS BLADDER FUNCTIONAL RESPONSES IN ANIMAL MODELS OF DETRUSOR OVERACTIVITY Vivian Cristofaro, Samar K. Lowalekar, Subbarao V. Yalla, and Maryrose P. Sullivan Vivian CristofaroVivian Cristofaro Boston, MA More articles by this author , Samar K. LowalekarSamar K. Lowalekar Boston, MA More articles by this author , Subbarao V. YallaSubbarao V. Yalla Boston, MA More articles by this author , and Maryrose P. SullivanMaryrose P. Sullivan Boston, MA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.338AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Loss of bladder smooth muscle (BSM) caveolae, membrane invaginations that modulate agonist-induced responses, may contribute to detrusor dysfunction. Reduction in caveolae was described in bladder outlet obstruction (BOO) and spontaneously hypertensive rats (SHR), two animal models with detrusor overactivity (DO). We investigated whether alteration in caveolar elements in BSM tissue from BOO and SHR results in abnormal regulation of contractile responses to physiologic agonists thus contributing to DO. METHODS BOO was created by placing a ligature around the proximal urethra of male Sprague Dawley (SD) rats for 2 weeks. Adult male SHR were used as a model of non-obstructive DO. Sham operated animals and Wistar Kyoto (WKY) rats served as controls respectively. Bladder tissue from each animal was stretched in organ bath at 37°C and the contractile responses induced by phenylephrine (PE), bradykinin (BK), and carbachol (CCh) were measured before and after caveolar depletion achieved by methyl-β-cyclodextrin (mβCD). The density of BSM caveolae and the distribution of caveolin (Cav) protein were compared among animals by electron microscopy and immunofluorescence respectively. RESULTS BSM caveolar density was significantly lower in BOO and SHR compared with sham and WKY. Cav-1, and Cav-3 protein expression decreased in BOO and SHR compared to their respective controls. mβCD significantly increased the contractile response to PE and BK in sham and WKY bladders, consistent with the negative regulation imparted by caveolae of these agonist responses. In BOO and SHR, the amplitudes of PE and BK contractions under baseline conditions were significantly higher compared to their respective controls, consistent with a loss of negative regulation due to the reduced caveolae. In addition, the effect of caveolar depletion on PE and BK responses in BOO and SHR was less effective. CCh-induced contractions were unaffected by mβCD in bladders from both DO models as well as in controls. CONCLUSIONS In normal bladders, several agonist-induced responses are negatively regulated by caveolae. In overactive bladders from BOO and SHR, a loss of caveolar elements is associated with significant alteration of contractile responses, suggesting an impaired negative regulation of these receptor-mediated responses. A decrease in caveolar elements seems to occur with DO independently from its etiology (secondary to obstruction or idiopathic) and may be potentially related to the development of this dysfunction © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e93 Peer Review Report Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Vivian Cristofaro Boston, MA More articles by this author Samar K. Lowalekar Boston, MA More articles by this author Subbarao V. Yalla Boston, MA More articles by this author Maryrose P. Sullivan Boston, MA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...