The effect of chronic partial bladder outlet obstruction on corpus cavernosum smooth muscle and Rho‐kinase in rabbits

Lin, Wei‐Yu; Mannikarottu, Anita; Chichester, Paul; Neuman, Paul; Johnson, A.; Pérez-Martínez, Francisco C.; Levin, Robert M.

doi:10.1002/nau.20607

Cited by 11 publications

(20 citation statements)

References 27 publications

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“…Other important contributing factors may include species differences, severity and duration of obstruction, degree of smooth muscle hypertrophy, and variability in methodological approaches. Despite the reported differences in contractile responses of the CCSM, all groups, including ours, detected a significant decrease in relaxation of CCSM strips isolated from PBOO animals (10,22,29). Impairment of CCSM relaxation was suggested to be associated primarily with upregulation of Rho-kinase expression/activity and changes in NO/NOS signaling (59).…”

Section: Discussioncontrasting

confidence: 52%

“…Other groups reported similar observations including diminished CCSM contractility under ischemic conditions resulted from occlusion of abdominal aorta in vivo (52). Lin et al (29) observed a decrease in the contractile response of the CCSM to Phe in a rabbit model of PBOO, whereas another group detected the opposite effect (10). Variability in contractility responses of the CCSM among the studies is likely associated with phasic molecular changes underlying adaptation of the CC muscle to new conditions induced by PBOO development.…”

Section: Discussionmentioning

confidence: 72%

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Bladder outlet obstruction triggers neural plasticity in sensory pathways and contributes to impaired sensitivity in erectile dysfunction

Malykhina

Chang

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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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.

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Section: Discussioncontrasting

confidence: 52%

Section: Discussionmentioning

confidence: 72%

Bladder outlet obstruction triggers neural plasticity in sensory pathways and contributes to impaired sensitivity in erectile dysfunction

Malykhina

Chang

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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“…[25] and Lin et al. [12], at a similar time point, possibly due to postoperative inflammation in the sham‐operated group and a reduction in CCSM cells, respectively. Results from chronic PBOO studies have revealed a time‐dependent change in the contractile response.…”

Section: Discussionmentioning

confidence: 70%

“…Lin et al. [12] found that the contractile response was reduced at 8 weeks, due to a reduction in CCSM content and an increase in collagen deposition.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II Increases Corpus Cavernosal Contractility and Oxidative Stress in Partial Bladder Outlet Obstructed Rabbits: Relevance to Erectile Dysfunction

Ertemi

Lau

Mikhailidis

et al. 2013

The Journal of Sexual Medicine

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Introduction We investigated the effect angiotensin II (Ang II), a corpus cavernosal smooth muscle (CCSM) constrictor peptide, has on tissue taken from rabbits following chronic partial bladder outlet obstruction (PBOO), as this model is characterized by an increase in corpus cavernosal collagen deposition and a marked reduction and impaired relaxation of CCSM cells. Aim To determine the interaction between Ang II and nitric oxide (NO) and the development of oxidative stress (OS) in a rabbit model of chronic PBOO. Methods Corpus cavernosal tissue was obtained from 12 sham-operated and 20 PBOO rabbits. Organ bath studies determined Ang II/NO interaction on CCSM function using losartan (AT1 receptor antagonist), sodium nitroprusside (SNP, NO donor), electrical field stimulation (EFS), and vardenafil (phosphodiesterase type 5 inhibitor). The role of OS in the Ang II response was also determined using diphenylene iodonium chloride (DPI), the nicotinamide adenine dinucleotide phosphate oxidase inhibitor, which inhibits superoxide production and superoxide dismutase (SOD, the enzyme that accelerates the breakdown of superoxide). Main Outcome Measure Action of Ang II and AT1 receptor antagonist, as well as SOD and DPI on CCSM function. Results Ang II caused a dose-dependent contraction of CCSM strips that was enhanced in PBOO rabbits and inhibited by losartan, DPI, and SOD. CCSM relaxation induced by SNP/EFS was impaired in this model and improved by vardenafil and losartan. Conclusions These findings imply that the increased Ang II contractile response is a pathological consequence of PBOO and that AT1 receptor inhibition may be a therapeutic approach to treat ED associated with PBOO.

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“…Thus, Rho‐kinase inhibitors would be therapeutically useful in BPH‐linked LUTS‐induced ED in men. Both ROCK activities increase at 2 and 8 weeks after PBOO, making the cavernosal smooth muscle more difficult to relax and decreases electrical field stimulation (EFS)‐induced relaxation of corpus cavernous smooth muscle (CCSM) [97]. The combination of the α1‐adrenoceptor antagonist doxazosin and the Rho‐kinase inhibitor Y‐27632 induce effective corpus cavernosum relaxation in the presence of PBOO in the rabbit [98].…”

Section: Rho‐kinase Pathway In Male Genital Organsmentioning

confidence: 99%

RhoA/Rho-Kinase as a Therapeutic Target for the Male Urogenital Tract

Gür¹,

Kadowitz²

2011

The Journal of Sexual Medicine

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Introduction Rho-kinase (ROCK) is a serine/threonine kinase and is one of the major downstream effectors of the small guanosine triphosphatase Rho. In the past few years, evidence has been accumulating to suggest that the RhoA/ROCK system may play an important role in the pathogenesis of a number of cardiovascular and urogenital disorders. Aim The aim of this study is to review the literature pertaining to the role of the RhoA/ROCK system in male urogenital function. Methods Comprehensive literature review was performed using PubMed. Main Outcome Measures Inhibitors of ROCK may have potential therapeutic applications, as derived from preclinical and a few clinical studies. Results Published reports suggest that elevated RhoA/Rho-kinase signaling plays a role in the development of benign prostatic hyperplasia, erectile dysfunction, kidney failure, ejaculation disorders, prostate and bladder cancer initiation, and eventual metastasis. Conclusions This review focuses on our current understanding of the role of the RhoA/Rho-kinase pathway in the regulation of the male urogenital system. Rho-kinase inhibitors may evolve into an important pharmacologic option in the future treatment of urogenital system disorders.

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The effect of chronic partial bladder outlet obstruction on corpus cavernosum smooth muscle and Rho‐kinase in rabbits

Cited by 11 publications

References 27 publications

Bladder outlet obstruction triggers neural plasticity in sensory pathways and contributes to impaired sensitivity in erectile dysfunction

Bladder outlet obstruction triggers neural plasticity in sensory pathways and contributes to impaired sensitivity in erectile dysfunction

Angiotensin II Increases Corpus Cavernosal Contractility and Oxidative Stress in Partial Bladder Outlet Obstructed Rabbits: Relevance to Erectile Dysfunction

RhoA/Rho-Kinase as a Therapeutic Target for the Male Urogenital Tract

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