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.

Effect of short‐ and long‐term sildenafil treatment on erectile dysfunction in rats with partial bladder outlet obstruction

“…Six weeks PBOO caused a more pronounced detrusor hypertrophy than obstruction for 3 weeks. This supports the recent data by Malykhina et al, 14 where partial obstruction of the bladder neck for 2 weeks induced a significant hypertrophy (2.5-fold increase) of the urinary bladder. In this study, the average bladder weight was 124 mg in sham-operated rats and 287 mg in animals with PBOO (132% increase).…”

“…This supports the recent data by Malykhina et al, where partial obstruction of the bladder neck for 2 weeks induced a significant hypertrophy (2.5‐fold increase) of the urinary bladder. In this study, the average bladder weight was 124 mg in sham‐operated rats and 287 mg in animals with PBOO (132% increase) . In another study by Yuan et al, the mean bladder weight was 14 mg for the young group, 37 and 70 mg for the PBOO‐3wk and ‐6wk group, respectively.…”

“…The partial bladder obstruction reduced the in vivo erectile response to CN stimulation. Bladder outlet obstruction may trigger nitrergic plasticity and hence impair erectile function . In fact, a central pathway coordinating bladder and corpus cavernosal function may exist.…”

“…Bladder outlet obstruction may trigger nitrergic plasticity and hence impair erectile function. 14 In fact, a central pathway coordinating bladder and corpus cavernosal function may exist. It is possible that the hypertrophic bladder may have a greater blood supply and nerve innervation than the erectile tissue.…”

Effects of silodosin, a selective alpha‐1A adrenoceptor antagonist, on erectile function in a rat model of partial bladder outlet obstruction

“…However, some studies demonstrated that the contractile responses of CC strips to Phe were decreased after PBOO . The finding that Phe‐induced contractions of CC is increased in PBOO but restored by silodosin appears harmonious.…”