Effect of Chronic Tadalafil Administration on Penile Hypoxia Induced by Cavernous Neurotomy in the Rat

Vignozzi, Linda; Filippi, Sandra; Morelli, Annamaria; Ambrosini, Stefano; Luconi, Michaela; Vannelli, Gabriella Barbara; Donati, Silvia; Crescioli, Clara; Zhang, Xinhua; Mirone, Vincenzo; Forti, Gianni; Maggi, Mario

doi:10.1111/j.1743-6109.2006.00208.x

Cited by 121 publications

(144 citation statements)

References 41 publications

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“…16 A parallel study by Vignozzi et al 37 also found that chronic tadalafil administration (120 days) to rats similarly reversed the decline in the cavernosal smooth muscle to collagen ratio that occurred after a bilateral cavernous neurotomy. Although Vignozzi et al hypothesized that the effect of the tadalafil may have been due to the reversal of hypoxia induced by the neurotomy, these studies taken together suggest that PDE5 inhibitors can potentially protect and preserve the integrity of the corpora after cavernosal nerve damage when given on a prolonged and continuous basis.…”

Section: Phosphodiesterase 5 Inhibitor Post-prostatectomymentioning

confidence: 80%

Rationale for phosphodiesterase 5 inhibitor use post-radical prostatectomy: experimental and clinical review

et al. 2007

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Erectile dysfunction (ED) is a common complication after radical prostatectomy and results from trauma sustained by the cavernosal nerves. This is a major concern for patients and often affects treatment decisions. The likely mechanism for post-prostatectomy ED is through corporal venoocclusive dysfunction. There is an increasing amount of evidence to suggest that phosphodiesterase 5 inhibitors (PDE5 inhibitors), when given on a continuous long-term basis, can help to prevent and reverse ED after surgery. In this review article we will examine the pathophysiology of postprostatectomy ED and discuss the experimental and available clinical evidence for administering PDE5 inhibitors after prostatectomy. Erectile dysfunction is common following radical prostatectomyRecent data suggest that approximately 161 000 men per year undergo a radical prostatectomy in the United States. 1 It is thought that many more men who are diagnosed with early-stage prostate cancer would accept this surgical form of treatment for their newly diagnosed disease if it were not for the possibility of the development of erectile dysfunction (ED). This common complication after radical prostatectomy is largely due to trauma sustained by the cavernosal nerves and is still widely encountered even after the most recent advances in surgical technique to spare the nerves. [2][3][4][5] Of men that are potent before surgery, only about 40-74% of men regain sexual function. [4][5][6][7] In fact, 41.9% of men reported that their sexual performance was a moderate to large problem after surgery 7 and patients appear to value sexual function so highly that they are often willing to choose therapy that offers better potency with lower life expectancy than options that offer longer life expectancy and lower potency rates. 8 Radical prostatectomy seems to disrupt and/or damage the neurovascular mechanisms responsible for eliciting an erection thereby resulting in either temporary or permanent ED postoperatively. In its mildest form, apparent in a successful bilateral nerve sparing prostatectomy, the trauma resulting from surgical manipulation of the neurovascular bundles may result in a neuropraxia leading to temporary ED. The most severe form of ED results from a non-nerve sparing prostatectomy where both nerves are transected, either volitionally or unrecognized at the time of surgery, and this leads to the complete loss of neuroregulatory functions in the corpora cavernosa. CVOD is the most common form of ED following radical prostatectomyInjury to the cavernosal nerves results in the atrophy and degradation of the underlying cavernosal smooth muscle, which, besides resulting in ED, may also lead to a decrease in penile weight. 9 Histologically, such a neuropraxia/neurotomy leads to apoptosis of the cavernosal smooth muscle and an excessive deposition of collagen within the cavernosa, which clinically results in corporal

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Section: Phosphodiesterase 5 Inhibitor Post-prostatectomymentioning

confidence: 80%

Rationale for phosphodiesterase 5 inhibitor use post-radical prostatectomy: experimental and clinical review

et al. 2007

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“…16 Chronic treatment with the phosphodiesterase type 5 inhibitor (PDE5i), tadalafil, prevented tissue hypo-oxygenation and ETB overexpression, although other biochemical alterations, such as NOS downregulation, were unaffected. 16 The aim of the present study was to define the time frame in which BCN induces penile hypoxia. In addition, we studied the time dependency of the effect of sildenafil, administered acutely 1 h before being killed, at a dose (25 mg/kg) known to significantly increase erections induced by electrical stimulation of the cavernous nerve.…”

Section: Introductionmentioning

confidence: 99%

“…4 An in vivo experimental model of penile prolonged hypoxia can be obtained in the rat by bilateral cavernous neurotomy (BCN), 14 which completely prevents spontaneous or apomorphine-induced erections 15 and, therefore, physiological penile re-oxygenations. 16 We previously demonstrated penile fibrosis and several biochemical alterations, including upregulation of ETB receptors, after 3 months of BCN. 16 Chronic treatment with the phosphodiesterase type 5 inhibitor (PDE5i), tadalafil, prevented tissue hypo-oxygenation and ETB overexpression, although other biochemical alterations, such as NOS downregulation, were unaffected.…”

Section: Introductionmentioning

confidence: 99%

“…16 We previously demonstrated penile fibrosis and several biochemical alterations, including upregulation of ETB receptors, after 3 months of BCN. 16 Chronic treatment with the phosphodiesterase type 5 inhibitor (PDE5i), tadalafil, prevented tissue hypo-oxygenation and ETB overexpression, although other biochemical alterations, such as NOS downregulation, were unaffected. 16 The aim of the present study was to define the time frame in which BCN induces penile hypoxia.…”

Section: Introductionmentioning

confidence: 99%

“…17 This study was designed to mimic molecular events occurring in the penis soon after sildenafil dosing after various time from radical retropubic prostatectomy. Penile hypoxia was evaluated as described previously by using the bio-reductive drug pimonidazole (Hypoxyprobe), 16 which has been recognized as a standard probe for in vivo imaging and quantification of hypoxia. 18 ETB expression and functional activity was evaluated using an originally described absolute quantitative reverse transcriptase polymerase chain reaction (RT-PCR) method and by evaluating 'in vitro' responsiveness to the selective ETB agonist IRL-1620.…”

Section: Introductionmentioning

confidence: 99%

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Effect of sildenafil administration on penile hypoxia induced by cavernous neurotomy in the rat

et al. 2007

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Hypoxia is a normal, physiological condition in penile tissue, which is interrupted by reoxygenation associated to sleep-related erections. We previously described in the rat that a penile fibrosis and overexpression of the pro-fibrotic endothelin-1 type B receptor (ETB) are associated to prolonged (3 months) hypoxia induced by the bilateral surgical resection of the cavernous nerves (bilateral cavernous neurotomy (BCN)). The aim of the present study was to define the time frame in which BCN induces hypoxia and ETB overexpression in the penile tissue. In addition, we studied the timedependency of the rescuing effect of an acute administration of the phosphodiesterase type 5 inhibitor, sildenafil. We found that BCN induced penile hypo-oxygenation (immunohistochemistry for Hypoxyprobe), penile ETB mRNA overexpression (quantitative real-time reverse transcriptase polymerase chain reaction) and hypersensitivity to the ETB agonist IRL-1620 (in vitro contractility study). Sildenafil treatment was able to counteract all these alterations (penile hypoxygenation, hyper-sensitivity to IRL-1620 and ETB overexpression), with its effect being more evident the earlier it was administered.

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Effects of the phosphodiesterase 5 inhibitor Tadalafil on bladder function in a rat model of partial bladder outlet obstruction

Kawai

Oka

Yoshinaga

et al. 2015

Neurourology and Urodynamics

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Effect of Chronic Tadalafil Administration on Penile Hypoxia Induced by Cavernous Neurotomy in the Rat

Cited by 121 publications

References 41 publications

Rationale for phosphodiesterase 5 inhibitor use post-radical prostatectomy: experimental and clinical review

Rationale for phosphodiesterase 5 inhibitor use post-radical prostatectomy: experimental and clinical review

Effect of sildenafil administration on penile hypoxia induced by cavernous neurotomy in the rat

Effects of the phosphodiesterase 5 inhibitor Tadalafil on bladder function in a rat model of partial bladder outlet obstruction

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