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DIFFERENTIAL EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH FACTOR IN OUTLET OBSTRUCTION VERSUS ESTROGEN-MEDIATED BLADDER HYPERTROPHY
Vol. 179, No. 4, Supplement, Sunday, May 18, 2008
Kit and vimentin as markers for ICs were performed on both BOO and control bladders. Morphological and functional properties of detrusor VPRRWK PXVFOH '60 ZHUH H[DPLQHG ZLWK ĮVPRRWK PXVFOH DFWLQ staining and intracellular recording, respectively. Electron microscopy was also carried out to characterise ultrastructural morphology of ICs. RESULTS: Two weeks after surgery, BOO animals showed an increased voiding frequency and a reduced voiding volume. Filling cystometry demonstrated a frequent incidence of non-voiding contractions, a reduced interval between voiding contractions and an increased voiding pressure in BOO bladders. In BOO bladders, the thickness of suburothelial and subserosal connective tissue layers was increased, whilst that of detrusor smooth muscle (DSM) layer was less affected. Population of Kit or vimentin immunoreactive ICs was increased in subserosal layers, and their distribution was altered in VXEXURWKHULDOOD\HULQ%22EODGGHUV1HLWKHUĮDFWLQLPPXQRUHDFWLYLW\ nor spontaneous electrical activity of DSM was altered in BOO bladders. ICs were characterised by their numerous mitochondria and caveolae, and had a close contact with each other and with neighbouring DSM or nerves. CONCLUSIONS: These results demonstrated the increased SRSXODWLRQRI,&VLQWKH%22JXLQHDSLJPRGHOIRUWKH¿UVWWLPHDQG suggest that the altered distribution of ICs may contribute to the pathophysiology of bladder overactivity. Source of Funding: Grants-in-Aids from Ministry of Education, Science, Sports and Cultureof Japan to Y.K.(No.19791117).
358 DIFFERENTIAL EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH FACTOR IN OUTLET OBSTRUCTION VERSUS ESTROGEN-MEDIATED BLADDER HYPERTROPHY Adam R Walker*, Matthew J Tanner, Catherine Schuler, Barry A Kogan, Robert M Levin, Ralph Buttyan. Albany, NY. INTRODUCTION AND OBJECTIVE: Both partial bladder outlet obstruction (PBOO) in male rabbits and ovariectomy (OVX) plus estrogen replacement in females lead to bladder hypertrophy. PBOO-mediated “dysfunctional” hypertrophy exhibits decreased contractile function, whereas estrogen-mediated “functional” hypertrophy exhibits increased contractile function. Vascular distribution is markedly different in the two models. Angiogenesis in PBOO-mediated hypertrophy is primarily submucosal and does not penetrate smooth muscle bundles, whereas angiogenesis occurring in estrogen-mediated hypertrophy occurs between and within smooth muscle bundles. To further elucidate these differences, we evaluated the expression of vascular endothelial growth factor (VEGF) in muscle and mucosa of hypertrophied bladders. 0(7+2'6 1HZ=HDODQGZKLWHUDEELWVZHUHGLYLGHGLQWR 7 groups: male control, 1-wk male PBOO, 2-wk male PBOO, female control, 1-wk OVX, 1-wk OVX plus 1-wk estrogen administration, and ZN 29; SOXV ZN HVWURJHQ DGPLQLVWUDWLRQ$IWHU VDFUL¿FH EODGGHU weights were measured, strips were taken for contractile studies, and remaining tissue was separated into muscle and mucosa. RNA was extracted from these tissues, and converted to cDNA via reversetranscriptase PCR. VEGF expression was then measured relative to GAPDH by real-time qPCR. RESULTS: Bladder weights were increased in the PBOO and estrogen replacement groups compared to controls. Contractile function was decreased in PBOO groups and increased in estrogen replacement groups, consistent with past results.The ratio of muscle/mucosa VEGF was elevated in both obstructed and estrogen-stimulated bladders at 1 week, but by 2 weeks, the obstruction group returned to baseline, and WKHHVWURJHQJURXSEHFDPHPDUNHGO\HOHYDWHG VHH¿JXUH
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&21&/86,216 2XUUHVXOWVVXJJHVWVLJQL¿FDQWGLIIHUHQFHV in the location of VEGF expression in the hypertrophied bladder, most strikingly demonstrated by the ratio of muscle/mucosa VEGF after 2 weeks of estrogen replacement. This may be an important factor in the development of functional versus dysfunctional bladder hypertrophy. Source of Funding: Department of Veteran’s Affairs, NIH Grant number RO-1-DK 067114.
359 VARDENAFIL IMPROVES BLADDER COMPLIANCE IN SPINAL CORD INJURED PATIENTS: RESULTS FROM A SINGLE DOSE, DOUBLE-BLIND PILOT STUDY Mauro Gacci*, Giulio Del Popolo, Angelo Macchiarella, Gianni Vittori, Alberto Lapini, Sergio Serni, Peter Sandner, Dieter Neuser, Mario Maggi, Marco Carini. Florence, Italy, and Wuppertal, Germany. INTRODUCTION AND OBJECTIVE: To evaluate, by urodynamic assessment, bladder compliance shift after a single 20 PJYDUGHQD¿ODGPLQLVWUDWLRQLQPDOH6SLQDO&RUG,QMXUHG 6&, SDWLHQWV under oxybutynin treatment. 0(7+2'6 :H SHUIRUPHG D VLQJOH FHQWUH UDQGRPL]HG double-blind, placebo controlled trial on 25 SCI patients with erectile dysfunction and micturition disorders. A baseline urodynamic test, and, later, a second urodynamic test 1 to 3 hours after administration of YDUGHQD¿OPJ FDVHV RUSODFHER FDVHV ZHUHSHUIRUPHG,QDOO patients, standard oral oxybutynin administration was not discontinued. Urodynamic assessment included maximum cystometric capacity (MCC) and maximum detrusor pressure during voiding (MDP) to calculate bladder compliance. 5(68/76 3ODFHERDGPLQLVWUDWLRQGLGQRWVLJQL¿FDQWO\DIIHFW HLWKHU0'3DQG0&&ZLWKQRFKDQJHLQFRPSOLDQFH$IWHUYDUGHQD¿O administration, maximum cystometric capacity considerably improved (233.5 vs. 272.0 ml, p<0.001), while maximum detrusor pressure during YRLGLQJZDVVLJQL¿FDQWO\UHGXFHG YVFP+2O, p<0.001). These changes generate a remarkable improvement in bladder compliance (4.3 vs.6.2 ml/cmH2O, p=0.003). Only 1 patients retained the same EODGGHUFRPSOLDQFHDIWHUYDUGHQD¿ODGPLQLVWUDWLRQ POFP+2O), while QRSDWLHQWVUHSRUWHGDFRPSOLDQFHGHFOLQH>VHH¿JXUHEHORZ@ CONCLUSIONS: We demonstrated that, in SCI patients, a VLQJOHPJYDUGHQD¿ODGPLQLVWUDWLRQDFKLHYHGDUHPDUNDEOHLQFUHDVHRI EODGGHUFRPSOLDQFH7KLVWULDOUHYHDOVIRUWKH¿UVWWLPHDXURG\QDPLFDOO\ recordable activity of PDE5I on human bladder. Further studies are necessary to investigate the potential role of PDE5I for neurogenic overactive bladder.
Source of Funding: None
Kit and vimentin as markers for ICs were performed on both BOO and control bladders. Morphological and functional properties of detrusor VPRRWK PXVFOH '60 ZHUH H[DPLQHG ZLWK ĮVPRRWK PXVFOH DFWLQ staining and intracellular recording, respectively. Electron microscopy was also carried out to characterise ultrastructural morphology of ICs. RESULTS: Two weeks after surgery, BOO animals showed an increased voiding frequency and a reduced voiding volume. Filling cystometry demonstrated a frequent incidence of non-voiding contractions, a reduced interval between voiding contractions and an increased voiding pressure in BOO bladders. In BOO bladders, the thickness of suburothelial and subserosal connective tissue layers was increased, whilst that of detrusor smooth muscle (DSM) layer was less affected. Population of Kit or vimentin immunoreactive ICs was increased in subserosal layers, and their distribution was altered in VXEXURWKHULDOOD\HULQ%22EODGGHUV1HLWKHUĮDFWLQLPPXQRUHDFWLYLW\ nor spontaneous electrical activity of DSM was altered in BOO bladders. ICs were characterised by their numerous mitochondria and caveolae, and had a close contact with each other and with neighbouring DSM or nerves. CONCLUSIONS: These results demonstrated the increased SRSXODWLRQRI,&VLQWKH%22JXLQHDSLJPRGHOIRUWKH¿UVWWLPHDQG suggest that the altered distribution of ICs may contribute to the pathophysiology of bladder overactivity. Source of Funding: Grants-in-Aids from Ministry of Education, Science, Sports and Cultureof Japan to Y.K.(No.19791117).
358 DIFFERENTIAL EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH FACTOR IN OUTLET OBSTRUCTION VERSUS ESTROGEN-MEDIATED BLADDER HYPERTROPHY Adam R Walker*, Matthew J Tanner, Catherine Schuler, Barry A Kogan, Robert M Levin, Ralph Buttyan. Albany, NY. INTRODUCTION AND OBJECTIVE: Both partial bladder outlet obstruction (PBOO) in male rabbits and ovariectomy (OVX) plus estrogen replacement in females lead to bladder hypertrophy. PBOO-mediated “dysfunctional” hypertrophy exhibits decreased contractile function, whereas estrogen-mediated “functional” hypertrophy exhibits increased contractile function. Vascular distribution is markedly different in the two models. Angiogenesis in PBOO-mediated hypertrophy is primarily submucosal and does not penetrate smooth muscle bundles, whereas angiogenesis occurring in estrogen-mediated hypertrophy occurs between and within smooth muscle bundles. To further elucidate these differences, we evaluated the expression of vascular endothelial growth factor (VEGF) in muscle and mucosa of hypertrophied bladders. 0(7+2'6 1HZ=HDODQGZKLWHUDEELWVZHUHGLYLGHGLQWR 7 groups: male control, 1-wk male PBOO, 2-wk male PBOO, female control, 1-wk OVX, 1-wk OVX plus 1-wk estrogen administration, and ZN 29; SOXV ZN HVWURJHQ DGPLQLVWUDWLRQ$IWHU VDFUL¿FH EODGGHU weights were measured, strips were taken for contractile studies, and remaining tissue was separated into muscle and mucosa. RNA was extracted from these tissues, and converted to cDNA via reversetranscriptase PCR. VEGF expression was then measured relative to GAPDH by real-time qPCR. RESULTS: Bladder weights were increased in the PBOO and estrogen replacement groups compared to controls. Contractile function was decreased in PBOO groups and increased in estrogen replacement groups, consistent with past results.The ratio of muscle/mucosa VEGF was elevated in both obstructed and estrogen-stimulated bladders at 1 week, but by 2 weeks, the obstruction group returned to baseline, and WKHHVWURJHQJURXSEHFDPHPDUNHGO\HOHYDWHG VHH¿JXUH
THE JOURNAL OF UROLOGY®
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&21&/86,216 2XUUHVXOWVVXJJHVWVLJQL¿FDQWGLIIHUHQFHV in the location of VEGF expression in the hypertrophied bladder, most strikingly demonstrated by the ratio of muscle/mucosa VEGF after 2 weeks of estrogen replacement. This may be an important factor in the development of functional versus dysfunctional bladder hypertrophy. Source of Funding: Department of Veteran’s Affairs, NIH Grant number RO-1-DK 067114.
359 VARDENAFIL IMPROVES BLADDER COMPLIANCE IN SPINAL CORD INJURED PATIENTS: RESULTS FROM A SINGLE DOSE, DOUBLE-BLIND PILOT STUDY Mauro Gacci*, Giulio Del Popolo, Angelo Macchiarella, Gianni Vittori, Alberto Lapini, Sergio Serni, Peter Sandner, Dieter Neuser, Mario Maggi, Marco Carini. Florence, Italy, and Wuppertal, Germany. INTRODUCTION AND OBJECTIVE: To evaluate, by urodynamic assessment, bladder compliance shift after a single 20 PJYDUGHQD¿ODGPLQLVWUDWLRQLQPDOH6SLQDO&RUG,QMXUHG 6&, SDWLHQWV under oxybutynin treatment. 0(7+2'6 :H SHUIRUPHG D VLQJOH FHQWUH UDQGRPL]HG double-blind, placebo controlled trial on 25 SCI patients with erectile dysfunction and micturition disorders. A baseline urodynamic test, and, later, a second urodynamic test 1 to 3 hours after administration of YDUGHQD¿OPJ FDVHV RUSODFHER FDVHV ZHUHSHUIRUPHG,QDOO patients, standard oral oxybutynin administration was not discontinued. Urodynamic assessment included maximum cystometric capacity (MCC) and maximum detrusor pressure during voiding (MDP) to calculate bladder compliance. 5(68/76 3ODFHERDGPLQLVWUDWLRQGLGQRWVLJQL¿FDQWO\DIIHFW HLWKHU0'3DQG0&&ZLWKQRFKDQJHLQFRPSOLDQFH$IWHUYDUGHQD¿O administration, maximum cystometric capacity considerably improved (233.5 vs. 272.0 ml, p<0.001), while maximum detrusor pressure during YRLGLQJZDVVLJQL¿FDQWO\UHGXFHG YVFP+2O, p<0.001). These changes generate a remarkable improvement in bladder compliance (4.3 vs.6.2 ml/cmH2O, p=0.003). Only 1 patients retained the same EODGGHUFRPSOLDQFHDIWHUYDUGHQD¿ODGPLQLVWUDWLRQ POFP+2O), while QRSDWLHQWVUHSRUWHGDFRPSOLDQFHGHFOLQH>VHH¿JXUHEHORZ@ CONCLUSIONS: We demonstrated that, in SCI patients, a VLQJOHPJYDUGHQD¿ODGPLQLVWUDWLRQDFKLHYHGDUHPDUNDEOHLQFUHDVHRI EODGGHUFRPSOLDQFH7KLVWULDOUHYHDOVIRUWKH¿UVWWLPHDXURG\QDPLFDOO\ recordable activity of PDE5I on human bladder. Further studies are necessary to investigate the potential role of PDE5I for neurogenic overactive bladder.
Source of Funding: None