Vol. 179, No. 4, Supplement, Monday, May 19, 2008 THE JOURNAL OF UROLOGY® 277

CONCLUSIONS: These data suggest that prophylactic use of INO-4885 helps prevent ED following radical prostatectomy.

Source of Funding: Inotek Pharmaceuticals.

796SUPERENZYME GENE THERAPY IMPROVED PENILE REHABILITATION IN RATS AFTER CAVERNOUS NERVE INJURY THROUGH ANTI-HYPOXIA AND ANTI-APOPTOTIC MECHANISMJiuhong Yuan*, O Lenaine Westney, Ke-he Ruan, Run Wang. Houston, TX.

INTRODUCTION AND OBJECTIVE: Erectile dysfunction (ED) is a very common complication after radical prostatectomy.

synthase activities that converts arachidonic acid directly to prostacyclin (PGI2). PGI2 is a potent smooth muscle (SM) relaxant. This study was

bilateral cavernous nerve crush (BCNC) rat penis to restore the penile erection.

METHODS: Forty adult Sprague-Dawley rats were randomly

Laser Doppler Imager on weekly basis. 28 days later, intracavernosal pressure (ICP) was recorded under cavernous nerve stimulation

was processed for Western blot analysis of total/phospho-Akt, eNOS,1

immunohistochemistry with quantitative image analysis for: ASMA, SM/collagen, collagen III/I, proliferating cell nuclear antigen (cell proliferation marker) and TUNEL (apoptotic index). Total collagen content was determined by hydroxyproline assay.

only and BCNC only. PGI2, eNOS & total/phospho-AKt expression levels 1

groups.

erectile function after cavernous nerve injury through anti-hypoxia and

provide therapeutic opportunities for ED caused by other diseases.Source of Funding: None

797THE EFFECT OF OXYTOCIN ANTAGONIST AND CALCIUM CHANNEL BLOCKER ON L-ARGININE- OR NMDA-INDUCED PENILE ERECTION THROUGH PARAVENTRICULAR NUCLEUS OF HYPOTHALAMUS IN THE RATKuang-Kuo Chen*, Luke S Chang. Taipei, Taiwan.

INTRODUCTION AND OBJECTIVE: Previous studies suggest that administration of N-methyl-D-aspartic acid (NMDA) or L-arginineinto paraventricular nucleus of hypothalamus (PVN) may induce a penile erection. NMDA induces penile erection by an increased nitric oxide synthase (NOS) activity. The NOS induced nitric oxide production and then stimulated oxytocinergic neurons releasing oxytocin which is calcium-dependent. The released oxytocin projects to extrahypothalamic brain areas to induce penile erection. Taken together, therefore the objective of this study is to investigate the effect of oxytocin antagonist and Ca2+ channel blocker (CCB) on L-arginine- or NMDA-induced penile erection through PVN in the rat.

METHODS: Male adult Sprague-Dawley rats were used. The intracavernous pressure (ICP) was recorded. Six groups of study were arranged as following: 1)stereotaxically delivery of oxytocin antagonist [d(CH2)5,Tyr(Me)2,Orn8

nl into intracerebral ventricle (ICV), followed by NMDA 50 ng/500 nl

pmol/500 nl into ICV, followed by NMDA 50 ng into PVN 15 minutes later, 3)saline injection 500 nl into ICV, followed by NMDA 50 ng into

PVN 15 minutes later, 4)administration of VASO 30 pmol/500nl into ICV, followed by L-arginine 500 nmol into PVN 15 minutes later, 5)application

into PVN 15 minutes later, and 6)saline injection 500 nl into ICV, followed by L-arginine 500 nmol into PVN 15 minutes later.

increase of ICP from 9.2 ± 2.1 mmHg to 74.3 ±10.0 mmHg with a duration of 101.7 seconds after administration of saline into ICV followed

increase of ICP from 10.0 ± 3.1 mmHg to 75.7 ± 7.4 mmHg with a duration of 28.4 minutes after administration of saline into ICV followed by PVN application of L-arginine.

CONCLUSIONS: The results of this study suggest that administration of either oxytocin antagonist or Ca2+ channel blocker

penile erection through PVN in the rat.Source of Funding: None

798COMPENSATORY CHANGES IN GENE EXPRESSION FOLLOWING siRNA KNOCK-DOWN OF MAXIK IN CORPORAL SMOOTH MUSCLE CELLSGiulia Calenda*, Arnold Melman, Kelvin P Davies. New York, NY.

INTRODUCTION AND OBJECTIVE: Erectile dysfunction (ED) is caused by alterations in the corporal smooth muscle (CSM)

modulation of intracavernous pressure. In general, these mechanisms

pathways. However, certain “key” genes appear to play a central role in the correct functioning of corporal smooth muscle tissue, such as the Slo gene encoding the MaxiK potassium channel. In Slo -/- knock-out mice where MaxiK is not expressed animals suffer from ED. Genetransfer of plasmids expressing MaxiK in both diabetic and ageing rats

present study we aimed to elucidate the interaction of MaxiK with other pathways involved in the contractile process of smooth muscle.

METHODS: We silenced the expression of MaxiK in cultured human CSM cells using siRNA against the hSlo gene. Total RNA

quantitative RT-PCR it was established that the expression of the Slo gene was decreased by more than 90% in the siRNA-treated cells. We

using the HG-133A GeneChip (Affymetrix). RESULTS: Microarray analysis demonstrated the most down-

regulated gene after hSlo-siRNA treatment was hSlo. However, several

up-regulated genes were CACNA1G and ARHGAP24. CACNA1Gencodes the alpha-subunit of the low voltage-activated T-type calcium channel subunit Cav3.1. T-type channels control calcium entry in excitable cells and Cav3.1 has been shown to be involved in regulation of intracellular calcium levels and regulation of myometrium smooth muscle contraction. ARHGAP24 codes for the Rho GTPase activating protein 24. Rho GTPase is an upstream regulator of Rho kinase that is involved in the modulation of contraction in smooth muscle tissues. Potentially these genes could compensate for the down-regulation of the Slo gene.

CONCLUSIONS: In summary, our data suggest that knock-down of MaxiK expression results in compensatory changes in expression of other genes. The role of MaxiK in regulating the smooth

different pathways.Source of Funding: NIH NIDDK.