Transcription of G-protein coupled receptors in corporeal smooth muscle is regulated by the endogenous neutral endopeptidase inhibitor sialorphin.

PURPOSE: Several reports suggest that the rat Vcsa1 gene is down-regulated in models of erectile dysfunction. The Vcsa protein product sialorphin is an endogenous neutral endopeptidase inhibitor and its down-regulation could result in prolonged activation of G-protein activated signaling pathways by their peptide agonists. We investigated whether Vcsa1 down-regulation could result in an adaptive change in GPCR (G-protein coupled receptor) expression. MATERIALS AND METHODS: Gene expression in cultured rat corporeal smooth muscle cells following treatment with siRNA directed against Vcsa1 or the neutral endopeptidase gene was analyzed using microarray and quantitative reverse transcriptase-polymerase chain reaction. In rats Vcsa1 is one of the most down-regulated genes following bilateral transection of the cavernous nerves. In that animal model we also investigated whether Vcsa1 down-regulation was accompanied by similar changes in gene expression in corporeal smooth muscle cells in which Vcsa1 was knocked down in vitro. RESULTS: Microarray analysis and quantitative reverse transcriptase-polymerase chain reaction demonstrated that corporeal smooth muscle cells treated in vitro with siRNA against Vcsa1 resulted in GPCR up-regulation as a functional group. In contrast, treatment of corporeal smooth muscle cells that lowered neutral endopeptidase activity resulted in decreased GPCR expression. These results suggest that the peptide product of Vcsa1, sialorphin, can effect GPCR expression by acting on neutral endopeptidase. In animals with bilaterally transected cavernous nerves the decreased Vcsa1 expression is accompanied by increased GPCR expression in cavernous tissue. CONCLUSIONS: These experiments suggest that the mechanism by which Vcsa1 modulates erectile function is partly mediated through changes in GPCR expression.

Case report: intrarenal arteriovenous fistula after ureteroscopic stone extraction with holmium laser lithotripsy.

A 79-year-old woman presented with gross hematuria 10 days after flexible ureteroscopic stone extraction with holmium laser lithotripsy. Work-up revealed a bleeding intrarenal arteriovenous fistula that was embolized. To our knowledge, this is the first report of this complication causing delayed hematuria after ureterorenoscopy.

Long-term results of the bulbourethral sling procedure.

PURPOSE: We evaluated the long-term efficacy of the male bulbourethral sling procedure in the treatment of post-radical prostatectomy urinary incontinence. MATERIALS AND METHODS: Between October 1994 and June 2000, 95 patients with post-radical prostatectomy incontinence underwent bulbourethral sling placement with tetrafluoroethylene bolsters at our hospital. Ultimately 71 of these patients responded to our questionnaire and they were classified into 2 groups. Group 1 consisted of 62 patients who had not undergone prior radiation therapy and group 2 consisted of 9 who had undergone radiation therapy before the sling procedure. Patients were asked to respond to questions regarding continence status as well as the validated Incontinence Quality of Life and International Prostate Symptom Score questionnaires. RESULTS: Mean followup from the most recent sling procedure was 4 years (range 0.27 to 6.55). Average patient age at questionnaire response was 74 years. A total of 86 procedures were performed on 71 patients. Of the 71 patients 7 underwent either sling removal or artificial urinary sphincter placement and were excluded from questionnaire analysis. Including retightening procedures 68% of the patients (72% of group 1, 43% of group 2) required 2 or less pads daily. Of the patients 36% (42% of group 1 and 14% of group 2) required 0 pads. CONCLUSIONS: The male bulbourethral sling procedure remains an effective treatment for post-prostatectomy incontinence at 4-year followup.