title: Bladder outlet obstruction triggers neural plasticity in sensory pathways and contributes to impaired sensitivity in erectile dysfunction.
abstract: Lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) are common problems in aging males worldwide. The objective of this work was to evaluate the effects of bladder neck nerve damage induced by partial bladder outlet obstruction (PBOO) on sensory innervation of the corpus cavernosum (CC) and CC smooth muscle (CCSM) using a rat model of PBOO induced by a partial ligation of the bladder neck. Retrograde labeling technique was used to label dorsal root ganglion (DRG) neurons that innervate the urinary bladder and CC. Contractility and relaxation of the CCSM was studied in vitro, and expression of nitric oxide synthase (NOS) was evaluated by Western blotting. Concentration of the sensory neuropeptides substance P (SP) and calcitonin gene-related peptide was measured by ELISA. Partial obstruction of the bladder neck caused a significant hypertrophy of the urinary bladders (2.5-fold increase at 2 wk). Analysis of L6-S2 DRG sections determined that sensory ganglia received input from both the urinary bladder and CC with 5-7% of all neurons double labeled from both organs. The contractile responses of CC muscle strips to KCl and phenylephrine were decreased after PBOO, followed by a reduced relaxation response to nitroprusside. A significant decrease in neuronal NOS expression, but not in endothelial NOS or protein kinase G (PKG-1), was detected in the CCSM of the obstructed animals. Additionally, PBOO caused some impairment to sensory nerves as evidenced by a fivefold downregulation of SP in the CC (P ≤ 0.001). Our results provide evidence that PBOO leads to the impairment of bladder neck afferent innervation followed by a decrease in CCSM relaxation, downregulation of nNOS expression, and reduced content of sensory neuropeptides in the CC smooth muscle. These results suggest that nerve damage in PBOO may contribute to LUTS-ED comorbidity and trigger secondary changes in the contraction/relaxation mechanisms of CCSM.
authors.affiliation: Division of Urology, Department of Surgery, University of Pennsylvania, Glenolden, PA, USA. Anna.Malykhina@uphs.upenn.edu
authors.forename: Anna P
authors.initials: AP
authors.lastname: Malykhina
authors.forename: Qi
authors.initials: Q
authors.lastname: Lei
authors.forename: Shaohua
authors.initials: S
authors.lastname: Chang
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Pan
authors.forename: Antonio N
authors.initials: AN
authors.lastname: Villamor
authors.forename: Ariana L
authors.initials: AL
authors.lastname: Smith
authors.forename: Allen D
authors.initials: AD
authors.lastname: Seftel
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D004195:Disease Models, Animal; D007172:Erectile Dysfunction / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D005727:Ganglia, Spinal / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009130:Muscle, Smooth / Q000294:innervation* / Q000378:metabolism / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D010413:Penis / Q000294:innervation* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000378:metabolism; D001743:Urinary Bladder / Q000294:innervation / Q000378:metabolism / Q000503:physiopathology; D001748:Urinary Bladder Neck Obstruction / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D013373:Substance P; D015740:Calcitonin Gene-Related Peptide
keywords: afferent innervation; corpus cavernosum; sensory neurons; smooth muscle contractility
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