Young Kyung Park

Renin Angiotensin System in Rabbit Corpus Cavernosum: Functional Characterization of Angiotensin II Receptors

PURPOSE The regulation of the corporal smooth muscle tone is important in the process of penile erection. Although specific angiotensin (ANG) II binding to and effects of ANG II on some reproductive structures have been studied, the presence of the renin-angiotensin system has not yet been defined in the corpus cavernosum. ANG II is formed from ANG I by angiotensin I-converting enzyme (ACE). ANG II and ANG I produce contractions in vascular smooth muscles. Two subtypes of ANG II receptors (AT1 and AT2) have been characterized. The purpose of the present experiments was to determine whether the renin-angiotensin system regulates rabbit corpus cavernosum smooth muscle tone. MATERIALS AND METHODS A strip of rabbit corpus cavernosum was mounted in an organ chamber to measure the isometric tension. The specific binding for 125I-ANG II was characterized by in vitro autoradiography. RESULTS ANG II and ANG I, precursor of ANG II, contracted corpus cavernosum smooth muscle dose-dependently, but the response of smooth muscle to ANG I was 10-fold less than that to ANG II. Contractile responses of smooth muscle to ANG II and ANG I were blocked by Dup 753, a specific inhibitor of ANG II type 1 receptor, but not by PD 123,319, a specific inhibitor of ANG II type 2 receptor. The effect of ANG I was attenuated by captopril, an inhibitor of ACE. Specific binding sites for 125I-ANG II were found in the corpus cavernosum. The dissociation constant (Kd) was 5.32 +/- 1.65 nM. and maximum binding capacity (Bmax) was 305.72 +/- 85.24 amol/mm. Specific binding of 125I-ANG II was displaced by Dup 753 (10(-6) M) but not by PD 123,319 (10(-5) M). The inhibitory constant (Ki) for Dup 753 was 8.09 +/- 2.51 nM. CONCLUSION The present results suggest that the renin-angiotensin system is involved in the regulation of corpus cavernosum smooth muscle tone of rabbit and the ANG II receptor subtype AT1 is important in the regulation of penile erection.

COMPARISON OF THE EFFICACY OF TVT AND TVT-O ON THE OVERACTIVE BLADDER SYMPTOMS IN WOMEN WITH STRESS URINARY INCONTINENCE

vs 2/26(7%), p=0.587). Symptom resolution was documented at 6 weeks post-operatively and was sustained at the mean follow up or 5.7 months (range 1-60 mo). CONCLUSIONS: In this retrospective cohort study, urodynamics confirmed obstruction in 54% with symptomatic voiding dysfunction after a sling procedure. The response to sling takedown was favorable and independent of urodynamic evidence of obstruction. Still, we believe urodynamics remains of value the evaluation of women with voiding dysfunction after anti-incontinence surgery in whom the decision for surgical intervention is often difficult if solely based on symptoms following sling surgery and supportive physical findings.

TARGETING BLADDER TUMOUR CELLS IN VIVO AND IN THE URINE BY A PEPTIDE IDENTIFIED USING PHAGE DISPLAY

10071 Background: Bladder cancer is one of the most common tumors of genitourinary tract. Selective delivery of drugs to tumor tissues is important for effective tumor therapy. Here we identified a peptide targeting bladder tumor cells using phage display. METHODS Phage peptide library containing CX7C (C-cysteine and X-any amino acid residue) was based on T7 415-1b phage vector (Novagen). Tumor xenografts were prepared by subcutaneously injecting BALB/c Nu/nu female nude mice with HT-1376 bladder tumor cells. For a carcinogen-induced tumor model, Fischer 344 female rats were supplied ad libitum with tap water containing 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) for 8 weeks. RESULTS A phage library containing CX7C random peptides was screened for selective binding to cells from human bladder tumor xenografts. Selected phage clones were individually evaluated for binding to cultured bladder tumor cells and for binding to cells from human tumor tissues of six patients. The peptide displayed by the most promising clone was synthesized and designated as Bld-1. Fluorescein-conjugated Bld-1 peptide showed selective binding to frozen sections of human bladder tumor tissues of three patients. In vivo tumor targeting was examined in a carcinogen-induced rat tumor model (n=20). When the fluorescent peptide was introduced into the bladder lumen, it selectively bound to tumor epithelium. Next, when the fluorescent peptide was intravenously injected into the tail vein, it homed to the bladder tumor, but was not detectable in normal bladder and control organs such as lung. Moreover, the fluorescent peptide bound to cells from urinary specimens of tumor patients (n=10), whereas little binding was observed in cells from healthy individuals (n=3). CONCLUSIONS The Bld-1 peptide may be useful for targeting bladder tumor cells in vivo and in the urine. No significant financial relationships to disclose.