These data indicate that the clinical effects of botulinum toxin A on the lower urinary tract may vary depending on the site of injection and level of nerve activity.

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Benign prostatic hyperplasia (BPH) is a serious health concern and is an underlying cause of lower urinary tract symptoms (LUTS) in many men. In affected men, LUTS/BPH is believed to result from benign proliferation of the prostate resulting in bladder outlet obstruction. Postnatal growth of the prostate is controlled via growth factor and endocrine mechanisms. However, little attention had been given to the function of the autonomic nervous system in prostate growth and differentiation. Nerve growth factor (NGF) is a prostatic mitogen that has a trophic role in autonomic sensory end organ interaction. In this study, we examine how the autonomic nervous system influences prostate growth as a function of age by quantifying NGF in the rat ventral prostate (VP) after pelvic ganglionectomy. Unilateral pelvic ganglionectomy was performed on postnatal days 30 (P30), 60 and 120 Sprague-Dawley rats in comparison to sham controls (n539). Semiquantitative RT-PCR, Western blotting and immunohistochemical analysis for NGF were performed on denervated, intact (contralateral side) and sham control VP 7 days after surgery. Ngf RNA expression was significantly increased in the denervated and intact hyperplastic VP. Western blotting showed age-dependent increases in NGF protein at P60 in the contralateral intact VP. NGF was localized in the nerves, basal cells and columnar epithelium of the prostatic ducts. Denervation causes age-dependent increases in NGF in the VP, which is a potential mechanism by which the autonomic nervous system may regulate prostate growth and lead to BPH/LUTS. Asian Journal of Andrology (2013) Keywords: denervation; nerve growth factor; prostate growth; ventral prostate INTRODUCTION Benign prostatic hyperplasia (BPH) is a serious health concern worldwide and is an underlying cause of many lower urinary tract symptoms (LUTS). LUTS is common in aging men and a population based survey performed in five countries reports that ,64% of adults experience at least one LUTS symptom.1 LUTS has a profound impact on social functioning and quality of life in affected men 2,3 with similar effects reported as after a heart attack or stroke.4 BPH can induce acute urinary retention, incontinence, recurrent urinary tract infection or obstructive uropathy. LUTS secondary to BPH generally consists of three components: benign proliferation of the stroma and epithelium, bladder outlet obstruction and symptoms resulting from obstruction.

The aim of this study was to investigate if the reduction in penile eNOS and erectile dysfunction in the streptozotocin (STZ) diabetic rat was related to RhoA!Rhokinase activation in the diabetic penile vascular bed.METHODS: Three groups of rats were utilized: 1) age matched control, 2) streptozotocin (STZ)-induced diabetic rats (60 mglkg ip) transfected with AAVCMV{3gal, and 3) STZ-rats with AAVCMVT19NRhoA (an inhibitor of RhoA). Confocal microscopy of Rho-kinase and eNOS was determined in the penis. Control and STZ-diabetic rats received intracavernous injections of the Rho-kinase inhibitor, Y-27632 (3-30 nmol). Seven days after transfection, rats underwent cavernosal nerve stimulation (CNS) to assess erectile function (peak intracavernosal pressure [ICP] and total ICP). Cavernosal RhoA, Rho-kinase, PhosThr696 MYPT-1 (a marker of Rho-kinase activity), eNOS and neuronal NOS (nNOS) protein (Western Blot), constitutive NOS activity (conversion of Larginine to L-citrulline ), and cGMP (EIA) levels were measured.RESULTS: Co-localization of Rho-kinase and eNOS was observed in the endothelium of the corpus cavernosum. There was an increase in erectile response to intracavernous injection of Y -27632 in STZ-rats that was greater than responses in control rats. There was a significant increase in RhoA, Rho-kinase, and MYPT -I phosphorylation in diabetic cavernosal tissue at a time when eNOS and nNOS protein, constitute NOS activity, and cGMP levels were decreased in the diabetic penis. Seven days after adena-associated viral gene transfer of TI 9NRhoA, there was a reduction in cavernosal RhoA, Rho-kinase, and MYPT-1 phosphorylation while cavernosal eNOS protein, constitutive NOS activity, and cGMP levels were increased. There was no change cavernosal nNOS. STZ-rats transfected with {3gal had significantly decreased erectile function as determined by CNS. The peak ICP and total ICP in response to CNS was significantly enhanced in STZ-rats transfected with T19NRhoA to a value similar to control rats.CONCLUSIONS: These data demonstrate a novel mechanism for the downregulation of eNOS in diabetes mediated by activation of the RhoA!Rho-kinase pathway. Importantly, these data imply that inhibition of RhoA!Rho-kinase improves eNOS protein and activity thus restoring endothelial and erectile function in diabetes.