Cyclic AMP regulates mRNA expression of alpha-1d and alpha-2a adrenergic receptors in cultured human corpus cavernosum smooth muscle cells

Traish, Abdulmaged M.; Kim, N N; Huang, Yuehua; Goldstein, Irwin; Moreland, Robert B.

doi:10.1038/sj.ijir.3900501

Cited by 10 publications

(6 citation statements)

References 14 publications

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“…Although both cAMP-and cGMP-mediated vasodilation can lead to corpus cavernosum smooth muscle relaxation and erection, combining the different mechanistic pathways may succeed where use of a single agent (cAMP or cGMP) fails. This may be in part due to high doses of PGE 1 -inducing contraction in the corpus cavernosum via thromboxane receptors 18 or inability of a single agent to overcome the norepinephrine-induced a-adrenergic mechanism in the penis in anxious patients. Furthermore, although neither MUSE nor sildenafil alone was sufficient to induce erection, blockade of both the cAMP and cGMP pathways may be a means of enhancing trabecular smooth muscle relaxation not unlike what has been reported for intracavernosal injection of single agents (for example, PGE 1 , papaverine) vs doubleagent and triple-agent modalities.…”

Section: Discussionmentioning

confidence: 99%

“…17 Increased cAMP may also dampen the aadrenergic response in corpora cavernosa by downregulating expression of contractile a-adrenergic receptors in the penis. 18 Finally, because this was a group of anxious patients, combination therapy may be much more efficacious in counteracting the potential increased adrenergic tone as a result of circulating catecholamines.…”

Section: Discussionmentioning

confidence: 99%

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Rationale for combination therapy of intraurethral prostaglandin E1 and sildenafil in the salvage of erectile dysfunction patients desiring noninvasive therapy

et al. 2002

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Corpus cavernosum smooth muscle relaxation and hence penile erection are regulated in part by increases in smooth muscle synthesis of the second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). The object of this study was to determine 30-month follow-up results in motivated patients desiring noninvasive medical therapy using sildenafil citrate (Viagra) in combination with intraurethral prostaglandin E 1 (PGE 1 ) (Medicated Urethral System for Erection [MUSE]). Twenty-eight patients (mean AE s.d. age, 59 AE 7.3 y; 17 who had undergone radical prostatectomy and 11 who had a diagnosis of organic erectile dysfunction) were included in this study. Detailed history taking and physical examinations were performed and vascular risk factors noted. In these patients, treatment with either 100 mg of sildenafil citrate and=or 1000 m mg of MUSE had failed. None of these patients desired intracavernosal injection. Duplex Doppler ultrasonography after redosing was carried out on all patients. Dynamic infusion corpus cavernosography=cavernosometry was obtained in 17 of 28 patients, and combination therapy was initiated using 100 mg of sildenafil citrate orally 60 min before intercourse and 500 m mg of MUSE intraurethrally immediately before intercourse. Independently, either 100 mg of sildenafil citrate or 1000 m mg of MUSE was not efficacious in inducing an erection sufficient for vaginal penetration in any of the 28 patients. After initiating a combination therapy, at 30 months, all 28 patients were reporting erections sufficient for vaginal penetration, with 3.6 intercourse episodes per month. None of the patients crossed over to intracavernosal therapy or penile prosthesis. During therapy, eight of 28 patients reduced the dose of sildenafil citrate to 50 mg. Combination therapy with MUSE and sildenafil may be more efficacious in the salvage of patients who desire noninvasive therapy but in whom single-treatment modalities fail. Although both cAMP-and cGMP-mediated vasodilation can lead to penile erection, combining therapies that incorporate both pathways may succeed when single therapies fail.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Rationale for combination therapy of intraurethral prostaglandin E1 and sildenafil in the salvage of erectile dysfunction patients desiring noninvasive therapy

et al. 2002

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“…Blockage of these receptors with ␣-receptor antagonists is often used to treat the symptoms of BPH (Price et al, 1993;Walden et al, 1999). Heightened pelvic sympathetic tone leads to elevated local norepinephrine levels, which act on the ␣receptors in the cavernous smooth muscle to stimulate contraction (Levin and Wein, 1980;Traish et al, 2000). The elevated local norepinephrine levels induce both vascular and cavernous smooth muscle contraction, producing an anti-erectogenic state.…”

Section: Receptors Luts and Bph-a Pathophysiologic Link?mentioning

confidence: 99%

The Link Between LUTS and ED: Clinical and Basic Science Evidence

Schiff

Mulhall

2004

Journal of Andrology

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Lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH) are extremely prevalent in aging men. LUTS describes the symptoms that occur with dysfunction of micturition. Both storage and emptying symptoms occur. Storage symptoms refer to urinary frequency, urgency, urge incontinence, nocturia, and dysuria. Emptying symptoms include hesitancy, straining, decreased force of stream, and incomplete emptying of the bladder, including urinary retention (Wein, 1981). BPH refers specifically to the histologic benign proliferation in the prostate gland, which may or may not be associated with LUTS.Erectile dysfunction (ED) is also an extremely common problem in older men. ED is defined as the consistent inability to maintain a penile erection sufficient for adequate sexual relations (NIH, 1993). The purpose of this review is to explore the link between the 2 conditions. Simply as a result of their predominance in older men, these 2 conditions are very likely to coexist. But is age the only link between LUTS and ED?Several other hypotheses exist that link LUTS and ED. First, some have postulated that the negative impact that LUTS has on the quality of life causes ED. Second, other studies have examined the role of a hyperadrenergic state in the pelvis associated with LUTS that adversely affects erectile function. Third, pharmacotherapy for BPH may affect erectile function. Finally, in the past, invasive therapy for BPH was thought to cause ED. This paper will explore the pathophysiologic link between LUTS and ED. Age, LUTS, and EDDefining BPH and LUTS-BPH is estimated to be present in 40% of men by age 50 and in more than 80% of men older than 80 years (Berry et al, 1984). On the basis of a prostate size in excess of 20 mL and a peak urinary flow rate of less than 15 mL/s, a Scottish study estimated that 14% of men in their 40s have BPH (Garraway et al, Correspondence to: Dr John P. Mulhall, 525 E 68th St, Starr 900, New York, NY 10021 (e-mail: jpm2005@med.cornell.edu).Received for publication September 23, 2003; accepted for publication March 29, 2004. 1991). This analysis also estimated that up to 43% of men older than 60 years have BPH. Definitions are important because, although the pathologic process is present within the prostate, many men are not symptomatically affected. Thus, even though BPH is frequently present in older men, the incidence of LUTS may be lower.An important contribution to our understanding of the progression of LUTS was provided by the Olmsted County Study. More than 2000 men aged 40-79 years were followed. Peak urinary flow was found to decrease by 2 mL/s each decade, and prostate size was estimated to increase by 0.6 mL/y. Those men with prostates greater than 40 mL were significantly more likely to suffer from LUTS. Men with large prostates were twice as likely to be bothered by their symptoms and also twice as likely to feel that their symptoms interfered with the activities of daily life (Girman et al, 1999). Moderate-to-severe LUTS has been found to occur in 8%-58% of men...

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“…Repeated intracavernous PGE1 injections have been reported to up‐regulate NO synthase expression in animal models (Escrig et al, 1999). An increase in cAMP is also shown to dampen the adrenergic receptors, which may be useful as these patients are more anxious with the failure of initial therapy (Traish et al, 2000). This mechanism may be the possible reason for MUSE combination being effective in salvaging the sildenafil failure cases in our study.…”

Section: Discussionmentioning

confidence: 99%

Combination Therapy: Medicated Urethral System for Erection Enhances Sexual Satisfaction in Sildenafil Citrate Failure Following Nerve‐Sparing Radical Prostatectomy

Raina

2005

Journal of Andrology

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ABSTRACT:The objective of our study was to assess the effectiveness of combining medicated urethral system for erection (MUSE) with sildenafil citrate in men unsatisfied with the sildenafil alone. Baseline and follow-up data from 23 patients (mean age, 62.5 Ϯ 5.23 years) unsatisfied with the use of the sildenafil citrate alone for the treatment of erectile dysfunction following nerve-sparing radical prostatectomy (mean use, 4 attempts/100-mg dose) was obtained. All patients started oral sildenafil citrate more than 6 months after radical prostatectomy. Combination therapy was initiated using 100 mg sildenafil citrate orally 1 hour prior to intercourse. Patients used combination therapy for a minimum of 4 attempts prior to assessment with the Sexual Health Inventory of Men (International Index for Erectile Function-5) and visual analog scale to gauge rigidity (0-100). The effect of therapy on the total International Index for Erectile Function (IIEF) score and penile rigidity score was assessed. Of the 23 patients, 4 (17%) had no improvement with the addition of medicated urethral system for erection and discontinued the drug, while 19 (83%) reported improvement with the penile rigidity and sexual satisfaction. The IIEF scores of these 19 patients showed significant improvements in each sexual domain, and the patients reported that erection was sufficient for vaginal penetration 80% of the time. Rigidity scores on a scale of 0-100 with sildenafil alone averaged 38% (23-53) for men and 46% (26-67) for their partners. With the addition of MUSE, scores increased to 76% for men and 62% for their partners. We conclude that the addition of MUSE to sildenafil improved sexual satisfaction and penile rigidity in patients unsatisfied with sildenafil alone.

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Cyclic AMP regulates mRNA expression of alpha-1d and alpha-2a adrenergic receptors in cultured human corpus cavernosum smooth muscle cells

Cited by 10 publications

References 14 publications

Rationale for combination therapy of intraurethral prostaglandin E1 and sildenafil in the salvage of erectile dysfunction patients desiring noninvasive therapy

Rationale for combination therapy of intraurethral prostaglandin E1 and sildenafil in the salvage of erectile dysfunction patients desiring noninvasive therapy

The Link Between LUTS and ED: Clinical and Basic Science Evidence

Combination Therapy: Medicated Urethral System for Erection Enhances Sexual Satisfaction in Sildenafil Citrate Failure Following Nerve‐Sparing Radical Prostatectomy

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