Objective: To investigate the changes in the α1-adrenoceptor and nerve growth factor (NGF)/NGF precursor (proNGF) pathway in the urethra after diabetes induction. Materials and Methods: Urethral relaxation function was determined by simultaneous recordings of intravesical pressure under isovolumetric conditions and urethral perfusion pressure (UPP) in diabetic rats. The expression of α1-adrenoceptor, NGF, proNGF, low-affinity p75 receptor for neurotrophins (p75NTR) and sortilin in the urethras was measured using real-time quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay and Western blotting. Results: In diabetic rats, the lowest urethral pressure (UPP nadir) during urethral relaxation was significantly higher. Intravenous administration of tamsulosin, an α1-adrenoceptor antagonist, significantly decreased the UPP nadir and baseline UPP in diabetic rats. RT-qPCR and Western blotting studies showed a statistically significant increase of α1a- and α1b-adrenoceptor in the urethras from the diabetic group (p < 0.05). The expression of NGF was significantly decreased in the urethras from the diabetic group while the expression of proNGF was significantly increased (p < 0.05). The p75NTR level in the urethras of diabetic rats was decreased compared with controls (p < 0.05) and there was no significant difference regarding sortilin between the two groups (p > 0.05). Conclusion: This study validated the diabetic urethral dysfunction and furthermore indicated that the increase in the expression of α1-adrenoceptor and changes in the NGF/proNGF pathway may be involved in diabetic urethral dysfunction.

Keywords:
Diabetes mellitus, Urethra, Alpha1-adrenoceptor, Nerve growth factor, Nerve growth factor precursor, Low-affinity p75 receptor for neurotrophins, Sortilin, Rats
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2014
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