Endothelial Rehabilitation: The Impact of Chronic PDE5 Inhibitors on Erectile Function and Protein Alterations in Cavernous Tissue of Diabetic Rats

Young, Ling Xu De; Domes, Trustin; Lim, KokBin; Carson, Jeffery J. L.; Brock, Gerald

doi:10.1016/j.eururo.2008.02.034

Cited by 48 publications

(35 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Finally, chronic treatment with PDE5-I has been associated with ameliorated endothelial function in both animal and human models. [40][41][42][43] Several mechanisms seem to be involved in the improvement of endothelial function after chronic PDE5-I administration. These include increased endothelial nitric oxide synthase activity, 44 decreased apoptotic cell death, 45 and an increased amount of circulating endothelial progenitor cells.…”

Section: Pharmacologic Prophylaxis Of Postoperative Erectile Dysfunctmentioning

confidence: 99%

Prediction of sexual function after radical prostatectomy

Briganti

Capitanio

Chun

et al. 2009

Cancer

View full text Add to dashboard Cite

Radical prostatectomy (RP) is a commonly used procedure in the treatment of clinically localized prostate cancer. For this report, the authors critically analyzed the factors associated with recovery of erectile function after surgery. A systematic review of the literature using the Medline and CancerLit databases was conducted. Keywords for the literature search included prostate cancer, radical prostatectomy, erectile dysfunction, impotence, treatment, and prophylaxis. Accurate patient selection (based on patient age, preoperative erectile function, and comorbidity profile) and adequate surgical technique (ie, the preservation of neurovascular bundles) were the major determinants of postoperative erectile function. Moreover, better results were achieved when an appropriate pharmacologic treatment using either oral or local approaches was given. Therefore, the authors concluded that, if patients are stratified correctly according to preoperative, intraoperative, and postoperative factors, then a satisfactory functional recovery may be expected after surgery. For these reasons, an ideal multivariate model predicting the restoration of erectile function after surgery should include patient, surgeon, and postsurgical treatment variables. The authors also concluded that the stratification of patients with regard to their risk of developing erectile dysfunction after surgery was feasible based on several parameters, which should be taken into account for correct patient treatment and counseling. To address this objective, accurate tools for predicting the likelihood of complete functional recovery after surgery are needed. Radical prostatectomy (RP) is used increasingly as a therapeutic option for patients who have clinically localized prostate cancer and a life expectancy 10 years. The pioneering work by Walsh and Donker 1 contributed significantly to our understanding of the surgical anatomy of the prostate and represented the basis for the subsequent development of the anatomic RP technique. The objective of this surgical approach is complete excision of the prostate to provide optimal cancer control while maintaining the integrity of the anatomic structures devoted to the functions of urinary continence and sexual potency. [2][3][4] Since the initial reports on this technique, increasing numbers of studies have reported satisfactory *Predictive Modeling in Prostate Cancer, Supplement to Cancer

show abstract

Section: Pharmacologic Prophylaxis Of Postoperative Erectile Dysfunctmentioning

confidence: 99%

Prediction of sexual function after radical prostatectomy

Briganti

Capitanio

Chun

et al. 2009

Cancer

View full text Add to dashboard Cite

show abstract

“…Chronic PDE5 inhibitor therapy has become increasingly popular. 18 There might be two major mechanisms involved: the first one is to connect organic etiology, such as improving endothelial function, 19 decreasing corporal fibrosis and veno-occlusive dysfunction. 20 The second mechanism may be the psychogenic factor.…”

Section: Discussionmentioning

confidence: 99%

Losartan improves erectile dysfunction in diabetic patients: a clinical trial

et al. 2012

View full text Add to dashboard Cite

The activation of cavernous local renin-angiotensin system has an important role in pathogenesis of diabetic erectile dysfunction (ED). In our primary study, we found that angiotensin Type 1 receptor blocker improved the erectile function of diabetic rats. Therefore we explored the losartan in clinical treatment for diabetic patients suffering with ED. A total of 124 diabetic patients with ED were included in this study and treated with losartan or tadalafil or losartan plus tadalafil or watch for waiting as control for 12 weeks. Erectile function was assessed by International Index of Erectile Function (IIEF-5) questionnaire, the percentage of positive responses to sexual encounter profile questions 2 (SEP2), 3 (SEP3) and the global assessment question (GAQ). Losartan or tadalafil or losartan plus tadalafil significantly improved the mean IIEF-5 scores, the percentage of successful penetrations (SEP2), the successful intercourse completions (SEP3) and GAQ (Po0.05). The combination of losartan and tadalafil is more effective than the single-use of losartan or tadalafil (Po0.05). The patients with moderate and mild ED had better response rates to losartan than patients with severe ED. This is the first clinical trial in losartan therapy on diabetic patients suffering from ED. Losartan seems to be effective and well-tolerated in diabetic ED patients, especially for mild to moderate ones. The combination therapy of losartan and tadalafil appeared to be more effective than monotherapy. Keywords: angiotensin type 1 receptor blocker; diabetes; erectile dysfunction; losarton; PDE5 inhibitor INTRODUCTION Erectile dysfunction (ED) is a common complication for diabetic patients. The pathogenesis of diabetic ED is multifactorial, involving the neural, vascular, endocrine and metabolic systems. 1,2 The first-line treatment for diabetic ED is phosphodiesterase Type 5 inhibitors. However, the efficacy of phosphodiesterase Type 5 inhibitors on diabetic ED is only about 51 --62%. 3 --5 Therefore, it is necessary to search for more effective medical therapies for this difficult condition.Our previous study showed that the angiotensin II (Ang II) level in the cavernosum of diabetic rats was much higher than that in normal controls. 6 Kifor et al. 7 reported that exogenous Ang II by ICI could terminate spontaneous erection in dogs, whereas administration of losartan, an Ang II receptor antagonist, resulted in smooth-muscle relaxation and erection. The inhibitor of local renin-angiotensin system (RAS) (angiotensinogen, (pro)renin receptor, angiotensin-converting enzyme, and angiotensin Type I (AT1) receptor ) of cavernosum in diabetic rats was obtained by administration of the angiotensin Type 1 receptor blocker (ARB), losartan. 8 Administration of losantan could also regulate human penile smooth muscle tone 9 and HO-1 gene expression 10 and improves erectile function in diabetic rats. 8 ARBs, a class of selective inhibitors of AT1, such as losartan, valsartan and irbesartan, are medications commonly used for cardiovascular diseas...

show abstract

“…In a similar study, Park et al 17 reported that chronic treatment with PDE5 inhibitor (SK-3530) activated Akt signaling, which lead to suppression of pro-apoptotic stimuli and maintained erectile function in a rat model of diabetic erectile dysfunction. Furthermore, De Young et al 18 investigated the effect of chronic administration on erectile function in a diabetic rat model. The authors reported that vardenafil was effective in treating diabetic-induced ED with the greatest effect achieved through chronic dosing.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic effect of combination of alagebrium (ALT-711) and sildenafil on erectile function in diabetic rats

et al. 2011

View full text Add to dashboard Cite

Recently, the relationship between advanced glycation end products (AGEs) and erectile dysfunction (ED) has been reported. The present study aimed to investigate whether a combination of an AGE cross-link breaker (alagebrium/ALT-711) and sildenafil could enhance the erectile capacity in streptozotocin (STZ) diabetic rats. Additionally, we assessed the effect of that treatment option on some molecules that have been suggested to have crucial roles in AGE-related ED pathways. Four groups of animals were utilized: (1) age-matched control rats, (2) STZ-induced diabetic rats (40 mg kg À1 i.p.), (3) STZ rats þ sildenafil (5 mg kg À1 p.o.), (4) STZ rats treated with a combination of sildenafil (5 mg kg À1 p.o) þ alagebrium/ALT-711 (10 mg kg À1 p.o.) for the final 1 month of the 2 months of diabetes period. At 2 months after i.p. injection of STZ, all animals underwent cavernosal nerve stimulation (CNS) to assess erectile function. Penile tissue AGEs, MDA (malondialdehyde), cyclic guanosine monophosphate (cGMP) (ELISA), endothelial nitric oxide (NO) synthase (eNOS), inducible NO synthase (iNOS) (western blot), nuclear factor (NF)-kB, mitogen-activated protein (MAP) kinase (immunohistochemistry) and apoptosis (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling) analyses were performed in all groups of rats. STZ diabetic rats had a significant decrease in erectile function as determined by the peak intracavernosal pressure (ICP) and total ICP (area under the erectile curve) after CNS when compared with control rats (Po0.05). The increase in both ICP and area under the erectile curve of STZ diabetic rats treated with a combination of sildenafil þ alagebrium/ALT-711 as well as in STZ diabetic rats treated with sildenafil alone was significantly greater than STZ diabetic rats. Additionally, combination treatment decreased AGE, MDA, iNOS, NF-kB, MAP kinase and apoptosis levels, whereas it preserved cGMP contents in diabetic penile tissue. Decreased AGE, MDA, iNOS, NF-kB, MAP kinase and increased cGMP levels at the combination (sildenafil þ alagebrium/ALT-711) therapy group increased both the peak ICP and total ICP to CNS in the STZ diabetic rats, which was similar to the response observed in control rats. These results may explain the role of AGEs in diabetes-related ED and the effect of an AGE cross-link breaker alagebrium/ ALT-711 þ sildenafil therapy on some critical molecules related to AGE-related ED pathways.

show abstract

Endothelial Rehabilitation: The Impact of Chronic PDE5 Inhibitors on Erectile Function and Protein Alterations in Cavernous Tissue of Diabetic Rats

Cited by 48 publications

References 29 publications

Prediction of sexual function after radical prostatectomy

Prediction of sexual function after radical prostatectomy

Losartan improves erectile dysfunction in diabetic patients: a clinical trial

Therapeutic effect of combination of alagebrium (ALT-711) and sildenafil on erectile function in diabetic rats

Contact Info

Product

Resources

About