ß3-Adrenoceptor Control of Lower Genitourinary Tract Organs and Function in Male: An Overview.

The sympathetic nervous system is one component of the nervous regulatory system of the physiological function of the lower genitourinary tract. Our knowledge on the role of this sympathetic system has advanced during the last decade due to the characterization of ß3-adrenoceptors (ß3-ARs) in the urogenital system. This review focuses on the pharmacological and molecular evidence supporting the functional roles of ß3-AR in male genitourinary tissues of various species. An electronic search in two different databases was performed including MEDLINE (PubMed) and EMBASE from 2010 to 2016. ß3-agonists may be a promising alternative to antimuscarinics in the treatment of overactive bladder (OAB) based on available evidence. Although more recent studies have evaluated the involvement of ß3-ARs in the physiological control and regulation of various tissues of the lower genitourinary tract mainly urinary bladder, penis, urethra, ureter, there are few innovations in the pipe-line. Among the ß3-agonists, mirabegron is a unique drug licensed for the treatment of patients with OAB. Many drugs classified as ß3-agonists are still under investigations for the treatment of OAB, lower urinary tract symptoms, ureteral stones, benign prostate hyperplasia, prostate cancer and erectile dysfunction. This review discusses the potential roles of ß3-AR as new therapeutic targets by evaluating the results of preclinical and clinical studies related to male lower genitourinary tract function. Looking into the future, the potential benefits of ß3- AR agonists from experimental and clinical investigations may provide an attractive therapeutic option.

Intracavernous Injection of Human Umbilical Cord Blood Mononuclear Cells Improves Erectile Dysfunction in Streptozotocin-Induced Diabetic Rats.

INTRODUCTION: Erectile dysfunction (ED) worsens in men with diabetes. Human umbilical cord blood (HUCB), because of its widespread availability and low immunogenicity, is a valuable source for stem cell-based therapies. AIM: To determine the effect of intracavernous injection of HUCB mononuclear cells (MNCs) on ED in rats with diabetes induced by streptozotocin. METHODS: Thirty adult male Sprague-Dawley rats were equally divided into three groups: (i) control, (ii) diabetes induced by streptozotocin (35 mg/kg intravenously for 8 weeks), and (iii) diabetic rats treated with MNCs (1 × 106 cells by intracavernosal injection). The HUCB-MNCs isolated by the Ficoll-Hypaque technique were obtained from eight healthy donors and administered to diabetic rats after 4 weeks. MAIN OUTCOME MEASURES: The ratio of intracavernosal pressure to mean arterial pressure ratio; the protein expression of endothelial and neuronal markers, such as von Willebrand factor, neuronal nitric oxide synthase, hypoxia-inducible factor-1α, and vascular endothelium growth factor; and the relative area of smooth muscle to collagen using western blotting and Masson trichrome staining were determined. RESULTS: Diabetic rats demonstrated a significantly decreased ratio of intracavernosal pressure to mean arterial pressure (0.26 ± 0.04; P < .01) and treatment with MNCs restored erectile function in diabetic rats (0.67 ± 0.05) compared with control rats (0.56 ± 0.02). In bath studies, neurogenic relaxant and contractile responses were significantly decreased in diabetic cavernosal tissues, which were restored by treatment. The ratio of smooth muscle to collagen was partly recovered by treatment, whereas von Willebrand factor levels were not altered in any group. Neuronal nitric oxide synthase and vascular endothelium growth factor levels were decreased, which were not restored by treatment. Increased hypoxia-inducible factor-1α protein expression in the diabetic group was completely normalized in MNC-treated diabetic samples. CONCLUSION: These results suggest that HUCB-MNC treatment can enhance the recovery of erectile function and promote numerous activities such the contribution of the hypoxia-inducible factor-1α and von Willebrand factor pathway to the neurogenic erectile response of diabetic rats. HUCB-MNCs in the healing process could involve an adaptive regenerative response and appear to be a potential candidate for cell-based therapy in ED of men with diabetes. It is evident that HUCB could provide a realistic therapeutic modality for the treatment of diabetic ED.